We assessed the effectiveness of the treatment supporter initiative as an intervention in improving clinic attendance for antiretroviral (ARV) drug refills and adherence to antiretroviral therapy (ART) in a cohort of HIV-infected adults. This two-arm randomized controlled trial was undertaken at an HIV clinic in a district hospital in Uganda. A total of 174 adult patients on ART were randomized 1:1 to a standard adherence intervention package plus a treatment supporter intervention (TS arm) or to a standard adherence intervention package (non-TS arm) alone. Clinic attendance for refills and adherence measurements using monthly clinic-based pill counts were monitored for both arms for 28 weeks. Baseline characteristics were similar for both arms. There was a non-significant difference in mean adherence between the TS and non-TS groups at end of follow-up [99.1% (95% CI: 98.3-99.9% vs. 96.3% (95% CI: 94.2-98.3%), P > 0.05]. TS participants had more than four times the odds of achieving optimal adherence (≥95%) [Odds ratio (OR) = 4.51, 95% CI: 1.22-16.62, exact P = 0.027]. TS participants were also more likely to be on time for their clinic appointments: 91.6 vs. 90.1% for TS and non-TS, respectively (OR = 1.19, 95% CI: 0.74-1.91, P > 0.05). Use of patient-selected treatment supporters may be an effective intervention to improve ARV treatment outcomes in resource-constrained settings.