AMENDMENT TO CONTRIBUTION AND PURCHASE AGREEMENT

Exhibit 2.1

AMENDMENT TO

CONTRIBUTION AND PURCHASE AGREEMENT

This AMENDMENT TO CONTRIBUTION AND PURCHASE AGREEMENT (this “Amendment”), executed on this 9th day of February, 2012, to be effective as of December 15, 2011, is by and among USMD Holdings, Inc., a Delaware corporation (“Holdings”), Urology Associates of North Texas, L.L.P., a Texas limited liability partnership (“UANT”), UANT Ventures, L.L.P., a Texas limited liability partnership (“Ventures”), and USMD Inc., a Texas corporation (“USMD”), and is joined in for limited purposes by John M. House, M.D. and Richard C. Johnston, M.D. Each of the parties to this Agreement is individually referred to herein as a “Party” and collectively, as the “Parties.” Capitalized terms used herein that are not otherwise defined herein shall have the meanings ascribed to them in Article IX of the Agreement (as defined below).

WHEREAS, the parties previously entered into that certain Contribution and Purchase Agreement dated August 19, 2010 (the “Agreement”); and

WHEREAS, before the Closing Date, UANT will merge with a wholly-owned subsidiary of Ventures, with UANT surviving and being a wholly-owned subsidiary of Ventures (the “UANT Merger”); and

WHEREAS, Ventures, Holdings, and MCNT are parties to an agreement (the “MCNT Agreement”), under which MCNT will merge with a wholly-owned subsidiary of Ventures before the Closing Date with MCNT surviving and being a wholly-owned subsidiary of Ventures (the “MCNT Merger”); and

WHEREAS, Ventures, Holdings, and Impel are parties to an agreement (the “Impel Agreement”), under which Impel will merge with a wholly-owned subsidiary of Ventures before the Closing Date with Impel surviving and being a wholly-owned subsidiary of Ventures (the “Impel Merger”); and

WHEREAS, the Contributing USMD Holders desire to, before the Closing Date, contribute at least a portion of their USMD shares directly to Ventures in exchange for partnership interests in Ventures, rather than first contributing them to Holdings; and

WHEREAS, the parties have decided that, at the Closing Date, Ventures shall contribute all of its assets, including its ownership interests in USMD, UANT, MCNT, and Impel, in exchange for shares of common stock in Holdings, thereby eliminating the promissory note described in the Agreement as a portion of the consideration to be received by Ventures; and

WHEREAS, the Parties desire to amend the Agreement in certain other respects;

NOW, THEREFORE, the Parties hereby agree as follows:

1. Contribution by Ventures. In lieu of the contribution described in Section 1.1 of the Agreement, Ventures agrees to contribute, assign, transfer, convey and deliver, or cause to be contributed, assigned, transferred, conveyed and delivered, all of its assets, including all of the equity interests in USMD, UANT, MCNT, and Impel to Holdings in exchange for the consideration described in paragraph 3 of this Amendment.

2. Contribution by USMD Holders. In lieu of the provisions in Section 1.2 of the Agreement, USMD agrees to cause the USMD Holders to contribute their USMD shares as follows:

(a) Those USMD Holders listed on Schedule I as “Contributing USMD Holders” shall, before the Closing Date, contribute their USMD shares (excluding the USMD shares referred to in subparagraph (b) of this paragraph 2) to Ventures in exchange for Class B Partnership Interests in Ventures (the “USMD-Ventures Contribution”);

(b) Each of those USMD Holders listed on Schedule I as “Contributing USMD Holders” shall contribute 57,985 USMD shares to Holdings in exchange for the consideration described in paragraph 3 of this Amendment; and

(c) Those USMD Holders listed on Schedule I as not being “Contributing USMD Holders” (the “Non-Contributing USMD Holders”) shall contribute all of their USMD shares to Holdings in exchange for the consideration described in paragraph 3 of this Amendment.

The contributions to Holdings by Ventures, the Contributing USMD Holders making contributions described in paragraph 2(b) of this Amendment, and the Non-Contributing USMD Holders are referred to herein as the “Contribution”.

3. Consideration. In lieu of the provisions in Section 1.4 of the Agreement, the Parties agree that the consideration for the Contribution shall be as follows:

(a) The aggregate consideration payable by Holdings for the Contribution shall be equal to 10,000,000 shares of common stock of Holdings (the “Holdings Shares”), of which (i) an aggregate of Nine Million (9,000,000) shares shall be issued to Ventures, the Contributing USMD Holders making contributions described in paragraph 2(b) of this Amendment, and the Non-Contributing USMD Holders at Closing in the amounts and to the persons set forth in Schedule I, which, for avoidance of doubt, shall be issued in proportion to the pro rata percentages set forth next to the name of each person set forth in Schedule I (the “Pro Rata Percentages”), and (ii) an aggregate of One Million (1,000,000) shares (the “Adjustment Shares”) shall be issued to John M. House, M.D. and Richard C. Johnston, M.D., as Nominees for Ventures, the Contributing USMD Holders making contributions described in paragraph 2(b) of this Amendment, and the Non-Contributing USMD Holders. The share certificate representing the Adjustment Shares shall be issued on the Closing Date but held by Holdings pending the adjustments described in subparagraph (b), below and shall be transferable only in accordance with subparagraph (e) below. The Adjustment Shares shall be shown as issued and outstanding on the balance sheet of Holdings on the date such shares are issued to John M. House, M.D. and Richard C. Johnston, M.D., as Nominees for Ventures, the Contributing USMD Holders making contributions described in paragraph 2(b) of this Amendment, and the Non-Contributing USMD Holders, and shall be legally outstanding under applicable state law.

(b) The allocation of the Adjustment Shares between Ventures, the Contributing USMD Holders making contributions described in paragraph 2(b) of this Amendment, and the Non-Contributing USMD Holders shall be determined following the Closing based upon changes in the relative value of the contributions to Holdings made by (i) Ventures (after accounting for the MCNT Merger, the Impel Merger, the UANT Merger and the USMD-Ventures Contribution), (ii) the Contributing USMD Holders making contributions described in paragraph 2(b) of this Amendment, and (iii) the Non-Contributing USMD Holders (it being agreed that the value of the contribution to Holdings made by the Contributing USMD Holders making contributions described in paragraph 2(b) of this Amendment and the Non-Contributing USMD Holders shall be based only on the value of USMD represented by the shares of common stock of USMD contributed to Holdings by the Contributing USMD Holders making contributions described in paragraph 2(b) of this Amendment the Non-Contributing USMD Holders pursuant to this Agreement and not that portion of the value of USMD contributed to Ventures by the Contributing USMD Holders pursuant to the USMD-Ventures Contribution), in each case between December 31, 2010 and 11:59 p.m. local time in Dallas, Texas on the Closing Date (the “Schedule 1.4 Adjustments”). For illustration only, Schedule I and Schedule 1.41 indicate that, on the Closing Date, 68,663 of the Adjustment Shares would be issued to the Contributing USMD Holders making contributions described in paragraph 2(b) of this Amendment and the Non-Contributing USMD Holders and 931,337 of the Adjustment Shares would be issued to Ventures. The relative consideration set forth in Schedule 1.41 has been derived in part from the fair market values of the respective business lines of USMD, Ventures, MCNT, and Impel as determined by valuations conducted by an independent third party valuation company.

The Schedule 1.4 Adjustments shall be calculated as follows:

(i) to reflect any changes since December 31, 2011 in “Total Subsidiary Level Debt,” “USMD Corporate Level Debt,” “Ventures/UANT Corporate Level Debt,” “Impel Level Debt,” and “MCNT Corporate Level Debt,” as set forth in Columns D, F, G, H, and I, respectively, of Schedule 1.41;

(ii) to reflect any changes since September 30, 2011 in ownership percentages of the assets or investments held by either USMD, Ventures/UANT, Impel, and MCNT, as reflected in Columns J, L, N, and P, respectively, of Schedule 1.41;

-2-

(iii) to reflect on Schedule 1.41 the amount of any “Deferred Payment Obligations” of USMD, Ventures/UANT, Impel, and MCNT as set forth in Cells K62, M62, O62, and Q62, respectively. Such amounts shall be calculated in accordance with the Schedule 1.4 Deferred Payment Obligations as defined in Article IX;

(iv) to reflect the amount of any “Net Working Capital Adjustments” of USMD, Ventures/UANT, Impel, and MCNT in Cells D75 of Schedule 1.42, D68 of Schedule 1.43, D75 of Schedule 1.44, and D75 of Schedule 1.45, respectively; and

(v) to reflect on Schedule 1.41 the amount of any mutually approved capital expenditures (A) since December 31, 2010 relating to fixed assets of the UANT clinical practice and (B) since September 30, 2011 relating to fixed assets or mutually approved capital contributions of USMD, Ventures/UANT, Impel, and MCNT as set forth in Cells K65, M65, O65, and Q65, including without limitation approved capital expenditures for equipment, building or tenant improvements.

(c) For the purposes of computing the adjustments, if any, pursuant to subsection (b) above, no adjustments to the Adjusted Equity Values reflected on Row 69 of Schedule 1.41 shall be made to the extent of any amounts already included in the calculations set forth in Rows 62-65 and Row 67 of Schedule 1.41, and the following provisions shall be applicable:

(i) No later than the later of (i) ninety (90) days following the Closing Date, or (ii) five (5) business days following the final determination of any adjustments to consideration under each of the MCNT Agreement and Impel Agreement, Ventures shall prepare and deliver to Holdings and the USMD Holder Representative a calculation of the Schedule 1.4 Adjustments, based upon its, and MCNT’s and Impel’s financial statements at and as of the Closing Date. Ventures shall provide the USMD Holder Representative, and Holdings shall provide to Ventures, any information and back-up materials reasonably requested by the requesting Party with respect to the Schedule 1.4 Adjustments.

(ii) The USMD Holder Representative shall have thirty (30) days following receipt of Ventures’s calculations of Schedule 1.4 Adjustments to notify Ventures of any dispute of any item contained therein, which notice shall set forth in reasonable detail the basis for such dispute. At any time within such thirty (30)-day period, the USMD Holder Representative shall be entitled to agree with any or all of the items set forth in Ventures’s calculation of the Schedule 1.4 Adjustments.

(iii) If the USMD Holder Representative does not notify Ventures of any such dispute within such thirty (30)-day period, or notifies Ventures of its agreement with Ventures’s calculations, Ventures’s calculations of the Schedule 1.4 Adjustments shall be final and binding on the Parties.

(iv) If the USMD Holder Representative notifies Ventures of any such dispute within such thirty (30)-day period, the Schedule 1.4 Adjustments shall be resolved as follows:

(A) The USMD Holder Representative and Ventures shall jointly determine the extent of any Schedule 1.4 Adjustments as promptly as practicable.

(B) In the event that the USMD Holder Representative and Ventures are unable to agree upon any of the Schedule 1.4 Adjustments, the Parties shall submit such matter to the Dallas, Texas office of Grant Thornton LLP (or if such firm is unwilling or unable to serve, another nationally recognizable accounting firm mutually agreed upon by the Parties), who shall make the final determination with respect to the correctness of the proposed Schedule 1.4 Adjustments in light of the terms and provisions of this Agreement, with such determination being final and binding on the Parties.

Notwithstanding anything herein to the contrary, the Schedule 1.4 Adjustments as set forth in subparagraphs (i) through (v) of paragraph 3(b) as they relate to MCNT and Impel shall be determined pursuant to each of the MCNT Agreement and Impel Agreement and shall be final and binding on the Parties hereto for purposes of any adjustments to the consideration made pursuant hereto.

(d) The allocation of the Adjustment Shares in accordance with this Section 1.4 shall be the Parties’ sole and exclusive basis for allocating Holdings Shares as a result of the relative values of the contributions to Holdings made by (i) Ventures (after accounting for the MCNT Merger, the Impel Merger, the UANT

-3-

Merger and the USMD-Ventures Contribution), (ii) the Contributing USMD Holders making contributions described in paragraph 2(b) of this Amendment, and (iii) the Non-Contributing USMD Holders. Any allocation of the Adjustment Shares in favor, or to detriment, of Ventures, the Contributing USMD Holders making contributions described in paragraph 2(b) of this Amendment, or the Non-Contributing USMD Holders shall be made in accordance with such Person’s Pro Rata Percentage.

(e) Once the allocation of the Adjustment Shares in accordance with this Section 1.4 has been finally determined, John M. House, M.D. and Richard C. Johnston, M.D. shall endorse the certificate representing the Adjustment Shares (or execute a separate stock power transferring such shares) to Ventures, the Contributing USMD Holders making contributions described in paragraph 2(b) of this Amendment, and the Non-Contributing USMD Holders in accordance with such determination, and Holdings shall deliver the certificate to its transfer agent with instructions to reissue the Adjustment Shares to Ventures, the Contributing USMD Holders making contributions described in paragraph 2(b) of this Amendment, and the Non-Contributing USMD Holders. In no event shall the reissuance of the Adjustment Shares to Ventures, the Contributing USMD Holders making contributions described in paragraph 2(b) of this Amendment, and the Non-Contributing USMD Holders occur later than five years following the Closing. Neither Ventures, the Contributing USMD Holders making contributions described in paragraph 2(b) of this Amendment, the Non-Contributing USMD Holders, Holdings, John M. House, M.D. nor Richard C. Johnston shall transfer, pledge, hypothecate or encumber any Adjustment Shares or rights to receive Adjustment Shares except that once the allocation of the Adjustment Shares in accordance with this Section 1.4 has been finally determined, they may transfer and allocate the Adjustment Shares in accordance with and pursuant to this Section 1.4.

(f) During the entire period the Adjustment Shares are held by John M. House, M.D. and Richard C. Johnston, M.D., as Nominees for Ventures, the Contributing USMD Holders making contributions described in paragraph 2(b) of this Amendment, and the Non-Contributing USMD Holders: (i) all dividends paid on any Adjustment Share will be distributed when received by John M. House, M.D. and Richard C. Johnston, M.D. to Ventures, the Contributing USMD Holders making contributions described in paragraph 2(b) of this Amendment, and the Non-Contributing USMD Holders in proportion to the Pro Rata Percentages and (ii) all voting rights of the Adjustment Shares shall be exercisable by John M. House, M.D. and Richard C. Johnston, M.D. at the direction of and on behalf of Ventures, the Contributing USMD Holders making contributions described in paragraph 2(b) of this Amendment, and the applicable Non-Contributing USMD Holders in proportion to the Pro Rata Percentages in the same manner as such shares would be entitled to such voting rights upon the reissuance of the Adjustment Shares to Ventures, the Contributing USMD Holders making contributions described in paragraph 2(b) of this Amendment, and the Non-Contributing USMD Holders under Section 1.4(e).

(g) This Section 3 of this Amendment and Section 1.4 of the Agreement are intended to comply with the requirements set forth in Section 2.02 of Revenue Procedure 84-42, 1984-1 C.B. 521.

4. Options. Section 1.7(b) of the Agreement is amended to read in its entirety as follows:

On the Closing Date, Holdings shall grant to Ventures options to purchase a number of shares of Holdings common stock equal to the number of shares of Holdings common stock that the holders of the USMD Granted Shares are entitled to receive pursuant to Section 1.7(a) above, at an exercise price equal to the quotient of (i) $3.00 divided by (ii) the Conversion Ratio. Such options shall expire five years from the date of issuance under the Holdings Equity Plan and shall be held by Ventures for the benefit of the Class A limited partners.

5. Tax Treatment. Section 11.6 of the Agreement is amended to read as follows:

The parties to this Amendment agree that, for United States federal income tax purposes the Contribution is intended to be, and shall be characterized as, an exchange qualifying under Section 351 of the Internal Revenue Code of 1986, as amended (the “Code”).

6. Issuance of Class B Partnership Interests. The Class B Partnership Interests in Ventures to be issued to the Contributing USMD Holders shall be based upon the relative values of the USMD shares contributed by them to Ventures as compared with the values of Ventures, UANT, MCNT, and Impel, as finally determined pursuant to this Amendment, the MCNT Agreement, and the Impel Agreement.

-4-

7. Additional Definition. “USMD Holder Representative” means John House, M. D.

8. Listing Application. Section 5.6 of the Agreement is amended to read as follows:

Holdings shall, as soon as practicable, prepare and submit to NASDAQ a listing application with respect to the listing on the Nasdaq Capital Market of the Holdings Shares issuable pursuant to the Contribution, and shall use its best efforts to obtain, prior to the Closing, approval for the listing of the Holdings Shares on the Nasdaq Capital Market, or another stock exchange agreed to in writing by the Parties, subject in either case to official notice of issuance.

9. Conditions Precedent to Obligations of USMD.

(a) Section 6.2 of the Agreement is amended to read as follows:

All of the representations and warranties made by Ventures, UANT and Holdings in this Agreement and in all certificates and other documents delivered by Ventures, UANT or Holdings to USMD pursuant hereto, shall have been true and correct in all material respects as of the date hereof, and shall be true and correct in all material respects at the Closing Date, with the same force and effect as if such representations and warranties had been made at and as of the Closing Date, except for changes permitted or contemplated by this Agreement, changes approved in writing by USMD and Holdings or any failure of any such representations and warranties to be true and correct in all material respects at the Closing Date solely as result of the consummation of the Impel Merger and/or the MCNT Merger on the Closing Date.

(b) Section 6.7 of the Agreement is amended to read as follows:

The S-4 Registration Statement shall have been declared effective by the SEC and NASDAQ shall have approved the listing on the Nasdaq Capital Market of the Holdings Shares issuable pursuant to the Contribution or such shares shall have been approved for listing on another stock exchange agreed to in writing by the Parties.

10. Conditions Precedent to Obligations of Ventures and UANT. Section 7.7 of the Agreement is amended to read as follows:

The S-4 Registration Statement shall have been declared effective by the SEC and NASDAQ shall have approved the listing on the Nasdaq Capital Market of the Holdings Shares issuable pursuant to the Contribution or such shares shall have been approved for listing on another stock exchange agreed to in writing by the Parties.

11. Subsequent Transfers of UANT Business Units. Section 8.9(b) of the Agreement is hereby deleted.

12. Survival of Representations, Warranties and Covenants. The first sentence of Section 8.12 of the Agreement is hereby deleted.

13. D&O Coverage. Holdings (or a third party at the direction of Holdings), at Holding’s sole expense, will pay at the Closing an amount sufficient to enable UANT to purchase “tail” coverage for a period of six (6) years following the Closing Date under the directors and officers liability insurance policy of UANT, as in effect on the Closing Date, up to an aggregate amount not to exceed $55,000.

14. New Definitions. The following definitions are added to Article IX of the Agreement:

“Impel” means Impel Management Services, L.L.C., a Texas limited liability Company.

“MCNT” means The Medical Clinic of North Texas, P.A., a Texas Professional Association.

“Schedule 1.4 Deferred Payment Obligations” means, in the case of UANT and Ventures, those certain deferred payments payable to Ken Licker, M.D.P.A., Robert Dowling, M.D.P.A., Gordon Brodie, M.D.P.A., and Mark Norris, M.D.P.A.

15. Revised Definitions. At Article X, the defined term, “Schedule III Deferred Payment Obligations” shall be deleted. In addition, the definitions of the defined terms below shall be revised so that such terms shall be defined as follows:

-5-

“Conversion Ratio” means the quotient of (a) the number set forth in Cell K72 of Schedule 1.41after the completion of the Schedule 1.41 Adjustments, divided by (b) the number of shares of USMD common stock outstanding immediately prior to the Closing.

“Outside Closing Date” means August 31, 2012.

16. Expenses. Section 8.2 of the Agreement is amended to read as follows:

8.2. Expenses. Except as provided in Section 8.1 and in the second paragraph of this Section 8.2, each Party shall pay its own expenses incurred in connection with this Agreement and the Transactions, whether or not the Agreement or the Transactions are consummated.

Holdings shall pay all filing fees in connection with all pre-transaction notifications required under the Hart-Scott-Rodino Antitrust Improvement Act of 1976, as amended, and the rules and regulations promulgated thereunder, in connection with the Transactions (including, without limitation, the UANT Merger, the MCNT Merger, and the Impel Merger).

[the rest of this page is blank]

-6-

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to Contribution and Purchase Agreement to be duly executed by their respective authorized signatories as of the date first indicated above.

-7-

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to Contribution and Purchase Agreement to be duly executed by their respective authorized signatories as of the date first indicated above.

-8-

Schedule I to Amendment to Contribution and Purchase Agreement

Schedule 1.41