Little is known about the effects of depression on adherence to medical treatment regimens in older patients with chronic medical illnesses. Poor adherence may explain the increased risk of medical morbidity and mortality found in depressed medical patients. Ten of 55 patients over the age of 64 with coronary artery disease met the criteria for major depression from the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.; American Psychiatric Association, 1987). All patients were prescribed a twice-per-day regimen of low dose aspirin to reduce their risk for myocardial infarction. Medication adherence was assessed for 3 weeks by an unobtrusive electronic monitoring device. Depressed patients adhered to the regimen on 45% of days, but nondepressed patients, on 69% (p < .02). Thus, major depression is associated with poor adherence to a regimen of prophylactic aspirin after the diagnosis of coronary artery disease.