Our objective was to determine the prevalence and identify the factors that influence antiretroviral therapy (ART) adherence among patients in Bamako and Ouagadougou. A cross-sectional study was conducted among 94 men and 176 women receiving ART. Data were collected through questionnaires and chart reviews. Logistic regressions were performed to isolate determinants of adherence. Overall, 58% of the patients were adherent, but there were differences in the levels of adherence according to country and treatment site. Sociodemographic factors were not associated with adherence. However, social characteristics such as having children, in Ouagadougou, or being a housewife and not planning to have a child in the next year, in Bamako were associated with adherence. Time on ART was negatively associated with adherence in both countries with decline occurring later in Bamako. Levels of adherence are inadequate particularly among more experienced patients. Further adherence research and monitoring using longitudinal designs are warranted to assess the extent to which adherence is declining with time on treatment.