Highly active antiretroviral therapy (HAART) can dramatically decrease human immunodeficiency virus (HIV) load in plasma, increase CD4+ cell counts, and prolong life for HIV-seropositive persons. However, the need for optimal adherence has been recognized. We implemented a pilot community-based program of directly observed therapy (DOT) with HAART among persons with substance use disorders and a history of failure of HAART. A near-peer outreach worker initially delivered and observed once-daily HAART doses on up to 7 days per week. Many participants tapered the frequency of visits. Participants were assessed by a brief questionnaire and determination of their CD4+ cell count and plasma HIV load. Twenty-five HIV-seropositive persons were enrolled and followed-up for a mean of 6.6 months (standard deviation, 3.9 months). We found that once-daily dosing of HAART by DOT is feasible in this population; in addition to observation of the majority of doses, most participants achieved virus suppression and felt favorably about the intervention. Tapering the intensity of visits with maximum flexibility was necessary to enhance the acceptability of the program to participants.