OBJECTIVE: To examine the contribution of medication adherence to 12-month depression scores in the context of other psychosocial and clinical predictors of depression in a sample of older adults treated for depression. METHODS: Secondary analysis of a prospective cohort study involving 241 older patients undergoing depression treatment using a standardized algorithm. Depression was measured at baseline and 12-months post-baseline. Baseline predictor variables included antidepressant adherence, barriers to antidepressant adherence, four domains of social support, basic and instrumental activities of daily living (BADLs and IADLs), and clinical factors including past history of depression and medical comorbidities. RESULTS: Nearly 28% of patients reported being nonadherent with their antidepressant medication. In bivariate analyses, greater antidepressant medication nonadherence, more medication barriers, poorer subjective social support, less non-family interaction, greater BADL and IADL limitations, poor self-rated health, higher baseline depression scores, and not having diabetes were related to higher 12-month depression scores. In multivariable analyses, greater medication nonadherence, not having diabetes, poorer subjective social support, greater BADL limitations, and higher baseline depression scores were related to higher 12-month depression scores. CONCLUSION: Interventions should be directed toward improving antidepressant adherence and modifiable psychosocial variables.