Background: Breakthrough direct-acting antivirals set a new standard in the management of hepatitis C virus (HCV) with regard to cure rates and improved tolerability; however, the health care system is challenged by the cost of these medications., Objective: To describe the effect of a comprehensive HCV medication management program on optimized regimen use, prior authorization (PA) modifications, and medication cost avoidance in a state Medicaid program., Methods: This program consists of a 2-tiered prescriber outreach: (1) regimen outreach to promote optimized regimen selection and (2) refill outreach to support medication adherence. PA criteria were developed to identify optimized regimens, taking into account member- and virus-specific factors as well as cost. Prescriber outreach was conducted to recommend the use of an optimized regimen as applicable. Successful regimen outreach was defined as the number of members for whom a recommendation was accepted. A refill report identified members without a subsequent paid HCV medication claim within 25 days of the previous claim and outreach to the prescriber's office was performed. The outcome measure for refill outreach was the number and type of PA modifications made secondary to outreach (closure or extension). Cost avoidance was calculated for members who completed treatment with an optimized regimen. Return on investment (ROI) was calculated for the program., Results: Between December 18, 2013, and January 31, 2015, 911 members had PA requests approved for simeprevir, sofosbuvir, or ledipasvir/ sofosbuvir. Of these members, 223 (24.5%) met the criteria for regimen outreach. Pharmacist interventions to treat with an optimized regimen were accepted for 135 members (60.5%). Following implementation of prescriber outreach to promote refills, between March 10, 2014, and January 31, 2015, offices were informed of an upcoming refill for 515 members. As a result of outreach, 19.6% of members had a subsequent PA modification. Sixty-nine approved PAs (for 68 members) were closed after correspondence with the prescriber, and 33 approved PAs (for 33 members) were extended. The total projected cost avoidance was $3,770,097. The comprehensive HCV medication management program demonstrated an ROI of $10.28 for every $1 spent., Conclusions: A comprehensive HCV medication management program can help contain costs while ensuring that members have access to most clinically appropriate regimens., Disclosures: No outside funding supported this study. Lavitas reports personal fees and nonfinancial support from University of Tennessee, Advanced Studies in Medicine and grant funding from Bristol-Myers Squibb, outside the submitted work. All other authors report no conflicts of interest. The poster "Overview of a Hepatitis C Medication Monitoring Program in a State Medicaid Program" was presented October 8, 2014, by Lavitas at the AMCP Nexus 2014 meeting in Boston, Massachusetts. A program update was presented at the 2015 American Drug Utilization Review Society Meeting on February 27, 2015. Study concept and design were contributed by Price, Lenz, and Jeffrey, with assistance from Lavitas, Tesell, and Hydery. Lavitas, Tesell, and Hydery collected the data, assisted by Price, Lenz, and Jeffrey, and data interpretation was performed by all authors. The manuscript was written by Greenwood, Lavitas, Tesell, and Hydery, with assistance from the other authors, and was revised by all authors.