© 2017, Springer Science+Business Media New York. We conducted a cluster-randomized trial to estimate effects of directly observed combination antiretroviral therapy (DOT-cART) on retention with viral suppression among HIV-positive adults in Peru. We randomly allocated facilities to receive the 12-month intervention plus the standard of care, including adherence support provided through accompaniment. In the intervention arm, health workers supervised doses, twice daily, and accompanied patients to appointments. Among 356 patients, intention-to-treat analyses showed no statistically significant benefit of DOT, relative to no-DOT, at 12 or 24 months (adjusted probability of primary outcome: 0.81 vs. 0.73 and 0.76 vs. 0.68, respectively). A statistically significant benefit of DOT was found in per-protocol and as-treated analyses at 12 months (0.83 for DOT vs. 0.73 for no DOT, p value: 0.02 per-protocol, 0.01 as-treated), but not 24 months. Rates of retention with viral suppression were high in both arms. Among adults receiving robust adherence support, the added effect of time-limited DOT, if any, is small-to-moderate.