IMPORTANCE: Progression of HIV disease, the transmission of the disease, and premature deaths among persons living with HIV (PLWH) have been attributed foremost to poor adherence to HIV medications. mHealth tools can be used to improve antiretroviral therapy (ART) adherence in PLWH and have the potential to improve therapeutic success. OBJECTIVE: To determine the efficacy of WiseApp, a user-centered design mHealth intervention to improve ART adherence and viral suppression in PLWH. DESIGN, SETTING, AND PARTICIPANTS: A randomized (1:1) controlled efficacy trial of the WiseApp intervention arm (n = 99) versus an attention control intervention arm (n = 101) among persons living with HIV who reported poor adherence to their treatment regimen and living in New York City. INTERVENTIONS: The WiseApp intervention includes the following components: testimonials of lived experiences, push-notification reminders, medication trackers, health surveys, chat rooms, and a "To-Do" list outlining tasks for the day. Both study arms also received the CleverCap pill bottle, with only the intervention group linking the pill bottle to WiseApp. RESULTS: We found a significant improvement in ART adherence in the intervention arm compared to the attention control arm from day 1 (69.7% vs 48.3%, OR = 2.5, 95% CI 1.4-3.5, P = .002) to day 59 (51.2% vs 37.2%, OR = 1.77, 95% CI 1.0-1.6, P = .05) of the study period. From day 60 to 120, the intervention arm had higher adherence rates, but the difference was not significant. In the secondary analyses, no difference in change from baseline to 3 or 6 months between the 2 arms was observed for all secondary outcomes. CONCLUSIONS: The WiseApp intervention initially improved ART adherence but did not have a sustained effect on outcomes.