Objective To test social cognitive predictors of medication adherence in racial/ethnic minority youth living with HIV using a conceptual model. Methods Youth were participants in two descriptive studies by the Adolescent Trials Network for HIV/AIDS Interventions. Minority youth ages 16–24 years who were prescribed antiretroviral medication were included (N = 956). Data were collected through chart extraction and/or laboratory testing and by Audio Computer-Assisted Self-Interview. Results 39% of youth reported suboptimal adherence. Path analysis was used to explore predictors of medication adherence. Higher self-efficacy predicted higher readiness and adherence. Greater social support predicted higher self-efficacy. Psychological symptoms and substance use were associated with several predictors and lower adherence. Conclusions The model provided a plausible framework for understanding adherence in this population. Culturally competent, but individually tailored, interventions focused on increasing self-efficacy to take medication and reducing risk behaviors (e.g., substance use) may be helpful for racial or ethnic minority youth with HIV.