We sought to test the efficacy of extended-release naltrexone (XR-NTX) on HIV-related and drinking outcomes. From April 2011-February 2015, we conducted a 4-site randomized double-blind placebo controlled clinical trial involving 51 HIV-positive patients with heavy drinking and < 95% antiretroviral (ART) adherence. All participants received counseling. The primary outcome was proportion with ≥ 95% ART adherence. Secondary outcomes included HIV biomarkers, VACS Index score, and past 30-day heavy drinking days. Based on receipt of ≥ 5 injections, 23 participants were retained at 24 weeks. We did not detect an effect of XR-NTX on ART adherence (p = 0.38); undetectable HIV viral load (p = 0.26); CD4 cell count (p = 0.75) or VACS Index score (p = 0.70). XR-NTX was associated with fewer heavy drinking days (p = 0.03). While XR-NTX decreases heavy drinking days, we did not detect improvements in ART adherence or HIV outcomes. Strategies to improve retention in alcohol treatment and HIV-related outcomes among heavy drinking HIV-positive patients are needed.