HIV-positive young Black MSM (YBMSM) experience poor antiretroviral (ART) medication adherence relative to their white counterparts. However, few studies have longitudinally examined factors that may correlate with various classifications of ART adherence among this population, which was the primary aim of this study. Project nGage was a randomized controlled trial conducted across five Chicago clinics from 2012–2015. Survey and medical records data were collected at baseline, 3-, and 12-month periods to assess psychological distress, HIV stigma, substance use, family acceptance, social support and self efficacy predicted ART medication adherence among 92 YBMSM ages 16 to 29 years old. Major results controlling for the potential effects of age, education level, employment, and intervention condition, indicated that participants with high versus low medication adherence were less likely to report daily/weekly alcohol or marijuana use, have higher family acceptance, and greater self efficacy. These findings identity important constructs that can be targeted in clinical and program interventions which correlate with improved ART medication adherence for YBMSM.