An embodied conversational agent can serve as a relational agent and provide information, motivation, and behavioral skills. To evaluate the feasibility, acceptability, and preliminary efficacy of My Personal Health Guide, a theory-based mobile-delivered embodied conversational agent intervention to improve adherence to antiretroviral therapy in young African American men who have sex with men, we conducted this prospective pilot study using a 3-month pre–post design. Outcome measures included adherence, acceptability, feasibility, pre versus post health literacy, and pre versus post self-efficacy. There were 43 participants. Pill count adherence > 80% improved from 62% at baseline to 88% at follow-up (p = .05). The acceptability of the app was high. Feasibility issues identified included loss of usage data from unplanned participant app deletion. Health literacy improved whereas self-efficacy was high at baseline and follow-up. This pilot study of My Personal Health Guide demonstrated acceptability and preliminary efficacy in improving adherence in this important population.