SecProbe.io

December  8, 2010

Richard King
President and Chief Executive Officer
AcelRx Pharmaceuticals, Inc.
575 Chesapeake Drive
Redwood City, CA 94063
Re: AcelRx  Pharmaceuticals, Inc.
Registration Statement on Form S -1
Filed November 12, 2010
  File No. 333 -170594
 Dear  Mr. King :

We have reviewed your registration statement and have the following comments.  In
some of our comments, we may ask you to provide us with information so we may better understand your disclosure.
 Please respond to this letter by am ending your registration statement and providing the
requested information.  If you do not believe our comments apply to your facts and
circumstances or do not believe an amendment is appropriate, please tell us why in your response.
 After reviewing any  amendment to your registration statement and the information you
provide in response to these comments, we may have additional comments.

General
1. Please note that when you file a pre -effective amendment containing pricing -related
information, we may ha ve additional comments.  As you are likely aware, you must file
this amendment prior to circulating the prospectus.

2. Please note that when you file a pre -effective amendment that includes your price range,
it must be bone fide. We interpret this to mean th at your range may not exceed $2 if you
price below $20 and 10% if you price above $20.

3. Please note that where we provide examples to illustrate what we mean by our comments, they are examples and not complete lists.  If our comments are applicable to portions of the filing that we have not cited as examples, please make the appropriate changes in accordance with our comments.

Richard King
AcelRx Pharmaceuticals, Inc.
December 8, 2010
Page 2

4. Please provide us proofs of all graphic, visual or photographic information you will
provide in the printed prospectus prior to i ts use.

5. Please provide an explanation of the following terms where you first use them:

• “bioadhesive excipient”
• “high oral transmucosal uptake”

 Sufentanil Nano Tabs , page 1
6. You disclose in the last paragraph of this subsection that you have one issued patent in
Europe.  Please expand your disclosure in the Prospectus Summary section to disclose that this patent is currently subject to opposition by third parties .

 Risks Associated with Our Business, page 5
7. Please expand your bulleted list of risks to al so state that the design for the device
component of your product candidates is still under development  and may not be fully
functional or commercially viable.

 Risk Factors, page 12
 We might be unable to service our current debt…, page 14
8. Please expand your disclosure to describe the installment payment due dates, the current
interest rate on the debt and amount of the installment payments, as well as the date when
the outstanding $6.4 million will become due.

 Our product candidates may cause adverse effects… , page 16
9. Please quantify the frequency or number of AEs o bserved in your clinical studies, as
compared to the subjects treated with placebo.

 We rely on limited sources of supply…, page 19
10. Please file copies of supplier agreements as exhibits an d describe the material terms of
the agreements in your filing or, alternatively, please tell us why you are not substantially
dependent on those suppliers.

 Our design for the device component of our product candidates …, page 20
11. Please expand you discl osure in the Business section to describe the stage of
development for each of your devices.

Richard King
AcelRx Pharmaceuticals, Inc.
December 8, 2010
Page 3

 Our future success depends on our ability to retain key executives…, page 26
12. Please expand your risk factor to disclose that each of your executive officers is
employed  “at-will.”

13. This risk factor addresses two separate risks:  (1) the risk of retaining key executives and
other qualified personnel; and (2) the risk that consultant and avisors may be employeed by others and may have commitments under consulting  or advisory contracts with other
entities that may limit their availability to the company.  Please separate the disclosure of these two risks under two appropriately titled risk factors.

Business, page 66
 ARX- 01 – Acute Post -Operative Pain, page 66
14. We note that you are using data from 2002 and 2003 for the percentage of errors resulting
in patient deaths.  Please update your disclosure with more recent data.

 Sufentanil NanoTab PCA System —ARX- 01 Clinical Program, page73
15. Please describe what you m ean by the “summed pain intensity difference” when you first
use this phrase.

 Sufentanil/Triazolan NanoTab —ARX- 03 Clinical Program, page 82
16. Please describe what you mean by “Richmond Agitation -Sedation Scale” when you first
use this phrase.

Intellectu al Property, page 84
17. Please expand your disclosure to provide the expiration date of the European Patent you
hold.  Also, with respect to this European Patent and the rest of the patent applications, please disclose what these patent and p atent applicatio ns relate to.

 Executive Compensation, page 105
 Cash Bonuses, page 111
18. We note that in connection with the hiring of Messrs. King and Welch the compensation committee approved annual cash bonus targets.  To the extent these bonuses will be paid based o n the achievement of performance goals set in advance, please describe the
performance goals.  To the extent quantifiable, please quantify the performance metrics.  Alternatively, if the bonuses will be awarded at the discretion of the board and no perform ance goals were set in advance, please disclose that fact.

Richard King
AcelRx Pharmaceuticals, Inc.
December 8, 2010
Page 4

 Long -Term Equity Incentive Awards, page 111
19. Please expand your disclosure to describe and quantify, to the extent quantifiable, the
corporate milestones and financial milestones that will resu lt in the grant of an option
covering 1% of the company for Mr. King and an option covering 100,000 shares for Mr. Welch.  Please also disclose when the achievement of these milestones will be measured.

 Notes to Financial Statements, page F -8
 Note 1.  Organization and Summary of Significant Accounting Policies, page F -8
 Liability Associated with Warrants to Purchase Convertible Preferred Stock, page F -12
20. You state that “changes in the estimated fair value of the convertible preferred stock
during the period are recorded through other income…”  Based on your other disclosures it appears that you are referring to your convertible preferred stock warrants.  Please revise your disclosures to refer to the convertible preferred stock warrants or further advise us about why changes in the estimated fair value of the convertible preferred stock
during the period are recorded in operations.

Note 7.  Warrants, page F -20
21. We note the fair values disclosed for the convertible preferred stock warrants at
December 3 1, 2008 and 2009, and September 30, 2010.  The total liabilities summed
from the disclosures ($10,000+ 986,000+ 1,200,000 = $2,196,000) do not equal that stated on the balance sheet for September 30, 2010 of $2,219,000.  Please revise your disclosures such that the total convertible preferred stock warrant liabilities are consistent with the balance sheet or further advise us about why these amounts do not equal.
 22. With regards to valuing your 2010 warrants to purchase Series C convertible preferred stock, y ou disclose that you evaluated multiple potential outcomes using the intrinsic
value or Black -Scholes value with multiple scenarios, and discounted the values back to
September 30, 2010.   Aside from the scenarios disclosed, please tell us what other scenarios were simulated in your evaluation of potential outcomes to determine a value for your warrants.  Also tell us how you evaluated the various outcomes from the scenarios to arrive at your final estimate for the 2010 warrant.  Additionally, please tell u s
what accounting literature was relied upon in making your determination that using the intrinsic value was appropriate for valuing your warrants.

Note 11.  Net Loss Per Share of Common Stock, page F -32
23. Please revise your disclosures for total convert ible preferred stock warrants such that
your quantitative disclosures and qualitative disclosures at note 7 for the total convertible

Richard King
AcelRx Pharmaceuticals, Inc.
December 8, 2010
Page 5

preferred stock warrants are consistent.  For example, at Note 5 and 7 you disclose that
10,000 convertible preferred stoc k warrants were issued in 2007 (Series A), 225,000 were
issued in 2008 (Series B), and 913,056 were issued in 2009 (Series C).  This disclosure is not consistent with your disclosures at page F -32 that 923,056 convertible preferred stock
warrants were outs tanding at December 31, 2008 and 2009, and for the nine months
ended September 30, 2009 and 2010.

24. Please revise your disclosure for the total “stock options to purchase common stock” outstanding at December 31, 2009 (2,657,500) to be consistent with the “ number of
shares underlying outstanding options” at Note 10 Stock- Based Compensation
(2,662,500) or further advise us about why these amounts should be different.

We urge all persons who are responsible for the accuracy and adequacy of the disclosure
in the filing to be certain that the filing includes the information the Securities Act of 1933 and
all applicable Securities Act rules require.   Since the company and its management are in
possession of all facts relating to a company’s disclosure, they are r esponsible for the accuracy
and adequacy of the disclosures they have made.

Notwithstanding our comments, in the event you request acceleration of the effective date
of the pending registration statement please provide a written statement from the compa ny
acknowledging that:

• should the Commission or the staff, acting pursuant to delegated authority, declare the
filing effective, it does not foreclose the Commission from taking any action with respect
to the filing;

• the action of the Commission or the staff, acting pursuant to delegated authority, in
declaring the filing effective, does not relieve the company from its full responsibility for
the adequacy and accuracy of the disclosure in the filing; and

• the company may not assert staff comments and t he declaration of effectiveness as a
defense in any proceeding initiated by the Commission or any person under the federal securities laws of the United States.

Please refer to Rules 460 and 461 regarding requests for acceleration.  We will consider a
written request for acceleration of the effective date of the registration statement as confirmation
of the fact that those requesting acceleration are aware of their respective responsibilities under the Securities Act of 1933 and the Securities Exchange Act of 1934 as they relate to the proposed public offering of the securities specified in the above registration statement.  Please allow adequate time for us to review any amendment prior to the requested effective date of the registration statement.

Richard King
AcelRx Pharmaceuticals, Inc.
December 8, 2010
Page 6

You may contact Christine Allen  at (202) 551 -3652 or Lisa Vanjoske  at (202) 551- 3614
if you have questions regarding comments on the financial statements and related matters.  Please contact Sebastian Gomez Abero  at (202) 551- 3578 or Dan Greenspan  at (202) 551 -3623
with any other questions.
Sincerely,

 Jeffrey P. Riedler
Assistant Director
 Cc: Mark B. Weeks
Chadwick L. Mills
Cooley LLP
3000 El Camino Real
Palo Alto, CA 94306- 2155