BACKGROUND: HIV continues to be a public health concern in Mexico and Latin America due to an increase in new infections, despite a decrease being observed globally. Treatment adherence is a pillar for achieving viral suppression. It prevents the spread of the disease at a community level and improves the quality and survival of people living with HIV. Thus, it is important to implement strategies to achieve sustained treatment adherence. OBJECTIVE: The objective of this study is to evaluate the effectiveness of a mobile health (mHealth) intervention based on SMS text messages to increase antiretroviral therapy (ART) adherence for HIV-positive adults. METHODS: A randomized controlled trial was performed at the Hospital Civil de Guadalajara - Fray Antonio Alcalde on HIV-positive adults who had initiated ART. The mHealth intervention included the use of SMS text messages as a reminder system for upcoming medical examinations and ART resupply to increase adherence. This intervention was provided to 40 participants for a 6-month period. A control group (n=40) received medical attention by the standard protocol used in the hospital. Intervention effectiveness was assessed by quantifying CD4+ T cells and viral load, as well as a self-report of adherence by the patient. RESULTS: The intervention group had greater adherence to ART than the control group (96% vs 92%; P<.001). In addition, the intervention group had better clinical characteristics, including a lower viral load (141 copies/mL vs 2413 copies/mL; P<.001) and a trend toward higher CD4+ T cells counts (399 cells/μL vs 290 cells/μL; P=.15). CONCLUSIONS: These results show that an mHealth intervention significantly improves ART adherence. Implementing mHealth programs could enhance the commitment of HIV-positive adults to their treatment.