OBJECTIVES: Approximately 1.1 million people in the U.S. are living with HIV, with 50,000 new infections per year.  The FDA approved Stribild™, a once-daily HIV medication, in September of 2012.  The primary objective of this study was to assess the cost and disease-related outcomes of Stribild versus guideline-recommended treatment options for HIV patients in a specialty retail pharmacy.  A secondary objective was to assess compliance via Medication Possession Ratios (MPRs). METHODS: HIV patients who were prescribed one of five antiretroviral regimens in the period from January 1, 2010 to June 21, 2013 and who obtained their medications through Schnucks Specialty Pharmacy were selected via a retrospective chart review.  By measuring the direct cost of the medications to the pharmacy and the disease-related outcomes, change in CD4 count and viral load suppression, the cost-effectiveness of Stribild versus its comparators was assessed.    RESULTS: A total of 92 patients were included in this study: 50 Stribild patients and 42 patients on alternate regimens: 15 Atripla®; 6 Isentress®; 10 Prezista®; and 11 Reyataz®.  Incremental Cost-Effectiveness Ratios (ICERs) were conducted between Stribild and the comparators for change in mean CD4 count and percent viral load suppression (<20 copies/ml) achieved.  In terms of CD4 count, Stribild was most cost-effective when compared to Prezista and least cost-effective when compared to Isentress.  Analyses of viral load suppression indicated that Stribild is more cost-effective than Prezista and Reyataz but less cost-effective than Atripla or Isentress.   Mean MPR was greater than 95% for Stribild and three of its comparators (not including Atripla); however, 78 percent of Stribild patients achieved MPR ≥ 95% which demonstrates higher compliance than all comparators except the Isentress patients.  CONCLUSIONS: The once-daily regimen Stribild appears effective at treating the HIV virus while maintaining compliance for most of its patients; its high cost remains a concern for formulary decision makers.