Objective: Although most agree that poor adherence to antiretrovirals is a common problem, relatively few factors have been shown to consistently predict treatment failure. In this study, a theoretical framework encompassing demographic characteristics, health beliefs/attitudes, treatment self-efficacy, and neurocognitive status was examined in relationship to highly active antiretroviral therapy adherence. Design: Prospective, cross-sectional observational design. Main Outcome Measures: Neuropsychological test performance, health beliefs and attitudes, and medication adherence tracked over a 1-month period using electronic monitoring technology (Medication Event Monitoring System caps). Results: The rate of poor adherence was twice as high among younger participants than with older participants (68% and 33%, respectively). Results of binary logistic regression revealed that low self-efficacy and lack of perceived treatment utility predicted poor adherence among younger individuals, whereas decreased levels of neurocognitive functioning remained the sole predictor of poor adherence among older participants. Conclusion: These data support components of the health beliefs model in predicting medication adherence among younger HIV-positive individuals. However, risk of adherence failure in those ages 50 years and older appears most related to neurocognitive status.