This study characterized rates and correlates of ART adherence in 242 HIV-infected persons 50+ years of age. Hierarchical regressions tested a model in which depression mediated the relationships between social support and avoidance coping with ART adherence. Results indicated low rates of consistent and timely adherence in both men (48%) and women (51%). For men and women alike, social support and avoidance coping predicted depression. Although rates of adherence and predictors of depression did not differ by gender, predictors of adherence did. Avoidance coping, social support and depression predicted ART adherence in older men, but not in older women. Contrary to expectations, depression did not mediate the relationships of coping and social support with ART adherence for either gender. These findings suggest that while HIV-infected older men and women share similar paths toward depression, they diverge in predictors of adherence. Adherence interventions may be more efficacious if they are sensitive to gender differences, although more research is first needed to identify factors related to adherence in HIV-infected older women.