Objective: Although antidepressants are an effective treatment for later-life depression, older patients often choose not to initiate or to discontinue medication treatment prematurely. Although racial differences in depression treatment preferences have been reported, little is known about racial differences in antidepressant medication adherence among older patients. Design: Prospective, observational study comparing antidepressant adherence for older African American and white primary care patients. Participants: A total of 188 subjects age 60 and older, diagnosed with clinically significant depression with a new recommendation for antidepressant treatment by their primary care physician. Measurement: Study participants were assessed at study entry and at the 4-month follow-up (encompassing the acute treatment phase). Depression medication adherence was based on a well-validated self-report measure. Results: At the 4-month follow-up, 61.2% of subjects reported that they were adherent to their antidepressant medication. In unadjusted and two of the three adjusted analyses, African American subjects (n = 82) had significantly lower rates of 4-month antidepressant adherence than white subjects (n = 106). African American women had the lowest adherence rates (44.4%) followed by African American men (56.8%), white men (65.3%), and white women (73.7%). In logistic regression models controlling for demographic, illness, and functional status variables, significant differences persisted between African American women and white women in reported 4-month antidepressant adherence (OR: 3.58, 95% CI: 1.27-10.07, Wald chi(2) = 2.42, df = 1, p < 0.02). Conclusions: The results demonstrate racial and gender differences in antidepressant adherence in older adults. Depression treatment interventions for older adults should take into account the potential impact of race and gender on adherence to prescribed medications.