SECOND AMENDMENT TO AMENDED AND RESTATED INVESTORS RIGHTS AGREEMENT

Exhibit 4.5

SECOND AMENDMENT TO AMENDED AND RESTATED

INVESTORS’ RIGHTS AGREEMENT

This SECOND AMENDMENT TO AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT (the “Amendment”), which amends the Amended and Restated Investors’ Rights Agreement, dated as of March 14, 2007, as further amended on November 12, 2007 (the “Rights Agreement”), by and among Data Domain, Inc., a Delaware corporation (the “Company”), and the investors listed on Schedule A thereto, is entered into this 15^th day of November, 2007 by and among the Company and holders of a majority of the Registrable Securities (as defined in the Rights Agreement), listed on the signature pages hereto, on behalf of all of the parties to the Rights Agreement.

RECITALS

WHEREAS, Section 3.7 of the Rights Agreement provides that any term of the Rights Agreement (other than Sections 2.1, 2.2 and 2.3) may be amended, and the observance of any provision therein waived, with the written consent of the Company and the holders of a majority of the Registrable Securities (as such term is defined in the Rights Agreement);

WHEREAS, Section 1.3 of the Rights Agreement sets forth the terms and conditions regarding the Company’s obligation to register under the Securities Act of 1933, as amended, Registrable Securities in connection with the Company’s registration and public offering of its securities;

WHEREAS, with respect to the Company’s proposed public offering of its common stock pursuant to the Company’s Registration Statement on Form S-1 filed with the Securities and Exchange Commission on November 1, 2007, Registration No. 333-147092, as amended, the Company and the holders of a majority of the Registrable Securities agree that such public offering should proceed with a different allocation of shares than would be prescribed under such Section 1.3 of the Rights Agreement; and

WHEREAS, the Company and holders of a majority of the Registrable Securities (as holders of a majority of the Registrable Securities of the Company) hereby desire to amend Section 1.3 of the Rights Agreement.

NOW, THEREFORE, in consideration of the foregoing recitals, mutual promises, and all other terms and conditions contained herein, the parties hereto hereby agree as follows:

AGREEMENT

1. Amendment of Section 1.3 of the Rights Agreement. The following clause shall replace Section 1.3(d) of the Rights Agreement in its entirety:

“(d) 2007 Piggyback Registration. Notwithstanding anything to the contrary in this Agreement, in connection with the public offering of shares of the Company’s common stock pursuant to the Company’s Registration Statement on Form S-1 initially filed with the Securities and Exchange Commission on November 1, 2007, Registration No. 333-147092, as amended (the “Follow-on Offering”), the allocation of Registrable Securities, together with the common stock held by certain other stockholders of the Company (and their affiliates) to be included in the Follow-on Offering shall be as follows:

(i) With respect to the firm portion of the Follow-on Offering in which the Company will issue and sell 2,800,000 shares of its common stock and certain stockholders of the Company (the “Selling Stockholders”) will offer and sell 3,200,000 shares of the Company’s common stock, the shares to be sold by the Selling Stockholders shall be allocated as follows:

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In the event that any of the Selling Stockholders are required to sell less than the number of shares listed in the table above or are excluded from participating in the Follow-on Offering because they are unable to provide the required documentation to enable participation in the Follow-on Offering or otherwise, the Chief Executive Officer and Chief Financial Officer of the Company may reallocate such shares to the other Selling Stockholders in their sole discretion such that the total amount sold shall continue to equal 3,200,000 shares.

(ii) With respect to the over-allotment portion (the “Over-Allotment Portion”) of the Follow-on Offering in which the Company will issue and sell 420,000 shares of its common stock and the Selling Stockholders will offer and sell 480,000 shares of the Company’s common stock, the shares to be sold by the Selling Stockholders shall be allocated as follows:

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In the event that any of the Selling Stockholders listed in the table above are required to sell less than the number of shares listed in the table above or are excluded from participating in the Follow-on Offering because they are unable to provide the required documentation to enable participation in the Follow-on Offering or otherwise, the Chief Executive Officer and Chief Financial Officer of the Company may reallocate such shares to the other Selling Stockholders in their sole discretion such that the total amount sold shall continue to equal 480,000 shares.

(iii) In the event that in connection with the Follow-on Offering, the underwriters do not fully exercise their over-allotment option such that less than an aggregate of 900,000 shares of the Company’s common stock are sold by the Company and the Selling Stockholders in the Over-Allotment Portion, the shares of Registrable common stock to be sold in the Over-Allotment Portion shall be reduced on a pro rata basis based upon the allocation of shares to the Company and the selling stockholders set forth in Section 1(c)(ii) above.

2. Rights Agreement. Except as expressly amended hereby, the Rights Agreement shall continue in full force and effect. In the event of any inconsistency or conflict between this Amendment and the Rights Agreement, the terms, conditions and provisions of this Amendment shall govern and control.

3. Entire Agreement. This Amendment and the Rights Agreement embody the complete agreement and understanding among the parties and supersede and preempt any prior understandings, agreements or representations by or among the parties, written or oral, which may have related to the subject matter hereof in any way.

4. Governing Law. This Amendment shall be governed by and construed under the laws of the State of California as applied to agreements among California residents entered into and to be performed entirely within California.

5. Counterparts. This Amendment may be executed in two or more counterparts, each of which shall be deemed to be an original, but all of which together shall constitute one and the same instrument.

REMAINDER OF THE PAGE INTENTIONALLY LEFT BLANK

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IN WITNESS WHEREOF, the parties have executed this Amendment as of the date first above written.

[Signature Page to Amendment to Data Domain, Inc.

Amended and Restated Investors’ Rights Agreement]

IN WITNESS WHEREOF, the parties have executed this Amendment as of the date first above written.

[Signature Page to Amendment to Data Domain, Inc.

Amended and Restated Investors’ Rights Agreement]