Depressive disorders have been shown to be associated with cardiac diseases and death, but the underlying disease mechanism is unclear. The authors hypothesized that the cardiac morbidity and mortality after depression in late life is mediated by subclinical atherosclerosis and is thus confined to ischemic heart diseases. Using the population-based cohort of the Longitudinal Aging Study Amsterdam, 2,403 men and women aged 55 and over without cardiac disease were followed to assess the onset of cardiac disease or cardiac death. Ischemic heart diseases (angina pectoris, [non]fatal myocardial infarction) were distinguished from other cardiac diseases (congestive heart failure, arrhythmia). Major depressive disorder (MDD) was defined according to Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III) criteria. Subthreshold depression was defined as clinically relevant depressive symptoms not fulfilling DSM criteria. After a mean follow up of 7.2 years, 444 first cardiac events occurred, of which 252 were primary ischemic events and 192 other cardiac events. Cox regression analysis adjusted for physical health variables showed that, when compared with nondepressed respondents, those with MDD had a relative risk (RR) of 2.09 (95% confidence interval: 1.13-3.85) for any cardiac event. Considering only ischemic events, the RR conferred by MDD increased to 3.00 (1.51-5.93), whereas the RR declined to 0.96 (0.24-3.89) for all other cardiac events. Subthreshold depression did not increase the risk of future cardiac events. Major depression in older age predicts first cardiac events. The excess cardiac morbidity and cardiac mortality after major depression could entirely be attributed to ischemic heart diseases.