OPKO Health Inc. — Director's Dealing 2015

Dec 28, 2015

STATEMENT OF CHANGES IN BENEFICIAL OWNERSHIP OF SECURITIES

Filed pursuant to Section 16(a) of the Securities Exchange Act of 1934 or Section 30(h) of the Investment Company Act of 1940

1. Name and Address of Reporting Person FROST PHILLIP M.D. ET AL

(Last) (First) (Middle) OPKO Health, Inc. 4400 Biscayne Blvd.

(Street) Miami FL 33137

(City) (State) (Zip)

1. Issuer Name and Ticker or Trading Symbol OPKO Health, Inc. [OPK]

2. Date of Earliest Transaction (Month/Day/Year) 12/24/2015

3. If Amendment, Date Original Filed (Month/Day/Year)

4. Relationship of Reporting Person(s) to Issuer (X) Director X 10% Owner (X) Officer (give title below) Other (specify below) CEO & Chairman

5. Individual or Joint/Group Filing (Check Applicable Line) (X) Form filed by One Reporting Person (X) Form filed by More than One Reporting Person

Table I - Non-Derivative Securities Acquired, Disposed of, or Beneficially Owned

1. Title of Security (Instr. 3)
2. Transaction Date (Month/Day/Year)
3. Transaction Code (Instr. 8)
4. Securities Acquired (A) or Disposed of (D) (Instr. 3, 4 and 5)
5. Amount of Securities Beneficially Owned Following Reported Transaction(s) (Instr. 3 and 4)
6. Ownership Form: Direct (D) or Indirect (I) (Instr. 4)
7. Nature of Indirect Beneficial Ownership (Instr. 4)

Common Stock 3,068,951 D

Common Stock 12/24/2015 P 2,700 A $10.08 158,397,043 I See Footnote (1)

Common Stock 12/24/2015 P 100 A $10.185 158,397,143 I See Footnote (1)

See

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| Common Stock | 12/24/2015 | P | 3,300 | A | $10.19 | 158,400,443 | I | Footnote (1) | | :--- | :--- | :--- | :--- | :--- | :--- | :--- | :--- | :--- | :--- | | Common Stock | 12/24/2015 | P | 1,300 | A | $10.195 | 158,401,743 | I | See Footnote (1) | | Common Stock | 12/24/2015 | P | 2,500 | A | $10.2 | 158,404,243 | I | See Footnote (1) | | Common Stock | | | | | | | 20,091,062 | I | See Footnote (2) |

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Table II - Derivative Securities Acquired, Disposed of, or Beneficially Owned (e.g., puts, calls, warrants, options, convertible securities)

1. Title of Derivative Security (Instr. 3)
2. Conversion or Exercise Price of Derivative Security
3. Transaction Date (Month/Day/Year)
4. Deemed Execution Date, if any (Month/Day/Year)
5. Number of Derivative Securities Acquired (A) or Disposed of (D) (Instr. 3, 4, and 5)
6. Date Exercisable and Expiration Date (Month/Day/Year)
7. Title and Amount of Underlying Securities (Instr. 3 and 4)
8. Price of Derivative Security (Instr. 5)
9. Number of Derivative Securities Beneficially Owned Following Reported Transaction(s) (Instr. 4)
10. Ownership Form of Derivative Security: Direct (D) or Indirect (I) (Instr. 4)
11. Nature of Indirect Beneficial Ownership (Instr. 4)

Reporting Owner Name / Address	Relationships	Director	10% Owner	Officer	Other
FROST PHILLIP M.D. ET AL OPKO Health, Inc. 4400 Biscayne Blvd. Miami, FL 33137	X	X	CEO & Chairman
Frost Gamma Investments Trust 4400 Biscayne Blvd. Miami, FL 33137		X

Explanation of Responses: (1) The securities are held by Frost Gamma Investments Trust, of which Phillip Frost M.D., is the trustee. Frost Gamma L.P. is the sole and exclusive beneficiary of Frost Gamma Investments Trust. Dr. Frost is one of two limited partners of Frost Gamma L.P. The general partner of Frost Gamma L.P. is Frost Gamma, Inc., and the sole shareholder of Frost Gamma, Inc. is Frost-Nevada Corporation. Dr. Frost is also the sole shareholder of Frost-Nevada Corporation. The reporting person disclaims beneficial ownership of these securities, except to the extent of any pecuniary interest therein and this report shall not be deemed an admission that the reporting person is the beneficial owner of these securities for purposes of Section 16 or for any other purpose.

(2) These securities are owned directly by The Frost Group, LLC. Frost Gamma Investments Trust is a principal member of The Frost Group, LLC.

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The reporting person disclaims beneficial ownership of these securities, except to the extent of any pecuniary interest therein and this report shall not be deemed an admission that the reporting person is the beneficial owner of these securities for purposes of Section 16 or for any other purpose.

Phillip Frost, M.D., Individually and as Trustee

12/28/2015

Signature of Reporting Person

Date

• If the form is filed by more than one reporting person, see Instruction 4(b)(v). ** Intentional misstatements or omissions of facts constitute Federal Criminal Violations. See 18 U.S.C. 1001 and 15 U.S.C. 78ff(a).

Note: File three copies of this Form, one of which must be manually signed. If space is insufficient, see Instruction 6 for procedure.

Potential persons who are to respond to the collection of information contained in this form are not required to respond unless the form displays a currently valid OMB number.

JOINT FILER INFORMATION

Name: Frost Gamma Investments Trust

Address: 4400 Biscayne Blvd. Miami, FL 33137

Designated Filer: Phillip Frost, M.D.

Issuer Name and Ticker Symbol: OPKO Health, Inc. (OPK)

Date of Earliest Transaction: December 24, 2015

Relationship to Issuer: 10% Owner

FROST GAMMA INVESTMENTS TRUST

By: /s/ Phillip Frost, M.D., as Trustee Phillip Frost, M.D., Trustee

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