Few epidemiologic studies have examined the association between depressive symptoms and atherosclerosis in subjects aged > or =65 years. Most of these studies were cross sectional and could not determine the temporality between depressive symptoms and the development of abnormal common carotid artery (CCA) intima-media thickness (CCA-IMT). To investigate the association between depressive symptoms and CCA atherosclerosis in subjects aged > or =65 years, data from 3,781 participants aged > or =65 years from the Cardiovascular Health Study were analyzed. The presence of depressive symptoms was measured by the Center for Epidemiologic Studies Depression Scale, while CCA-IMT as an indicator of CCA atherosclerosis was measured by B-mode carotid ultrasonography. Multivariate generalized estimation equations adjusted for age, gender, race, alcohol intake, blood glucose status, body mass index, and time showed that subjects aged > or =65 years with depressive symptoms had larger CCA-IMTs than those who did not have such symptoms (beta = 18.26 microm, SE 8.06, p = 0.03). Using 1,000 and 1,140 microm as cut-off points to exclude participants who had abnormal CCA-IMTs at baseline, the adjusted relative risks and the corresponding 95% confidence intervals of developing abnormal CCA-IMT over 3 years were 1.30 (95% confidence interval 1.10 to 1.44) and 1.21 (95% confidence interval 1.00 to 1.46), respectively. Similar results were obtained after excluding participants with prevalent cardiovascular disease at baseline. In conclusion, these data indicate that depressive symptoms are associated with the development of atherosclerosis in subjects aged > or =65 years.