Background: Human immunodeficiency virus (HIV) infection has become a disease in epidemiological transition since the introduction of antiretroviral therapy (ART); however, its control depends on adherence to therapy. There are some studies in Mexico regarding such adherence but they have had heterogeneous results. We aimed to determine the prevalence of ART adherence and risk factors associated with non-adherence among HIV-infected adults in a tertiary care hospital in Mexico. Methods: This was a cross-sectional study conducted at the Hospital de Infectología, "La Raza" National Medical Center, Mexico City. The subjects of the study were HIV-infected adults after at least 6 months on ART. They answered a questionnaire involving socio-demographics, biochemical, and clinical variables. Adherence was measured using the simplified medication adherence questionnaire Results: Three hundred seventy-six HIV-infected patients were included in the study. The median age was 35 years (interquartile range, IQR, 29-44) and most of them were men (79.3%). Among the participants, 73% (95% confidence interval, CI, 68.2-77.4%) adhered to the medications prescribed. Factors associated with good adherence were being male (odds ratio, OR, 0.43; 95% CI, 0.22-0.83) and the absence of alcohol use (OR, 0.27; 95% CI, 0.12-0.58); factors associated with non-adherence were a history of ≥2 ART regimens (OR, 1.95; 95% CI, 1.05-3.62), time spend attending medical care or receiving drugs (OR, 2.40; 95% CI, 1.22-4.70), and persistent viremia (OR, 2.72; 95% CI, 1.42-5.19; P<0.005). Conclusion: In the era of ART as prevention for transmission of HIV as well as treatment for HIV-positive individuals irrespective of CD4 cell counts, the importance of adherence has grown. Treatment failure reduces future treatment options and therefore long-term clinical success as well as increases the possibility of developing drug resistant mutations. Being male and a lack of alcohol use were factors associated with higher rates of adherence, whereas previous use of ART, more ARV regimens, and a longer time waiting for medical care or drugs, were associated with nonadherence in this HIV-infected population. Incomplete ART adherence is associated with persistent viremia. J o urnal o f A ID S & Cli n ic a l R es earc h