Medical mistrust is a significant barrier to medication adherence among African Americans living with HIV. In this study 380 African American people receiving antiretroviral therapy (ART) in a southern US city completed computerized measures at a community-based research site. Multiple mediation modeling showed that medical provider mistrust was associated with medication beliefs and ART adherence. Also, medication beliefs predicted adherence. The indirect effects of medical mistrust on adherence via medication beliefs was significant; the indirect effect was significant for medication concerns beliefs, but not medication necessity beliefs. Medication concerns beliefs therefore mediate the association between medical mistrust and ART adherence.