To investigate the association between baseline depressive symptoms and first fatal and non fatal coronary heart disease (CHD) and stroke in older adults, taking antidepressants and disability into account. In the Three City Study, a community-based prospective multicentric observational study cohort, 7,308 non-institutionalized men and women aged ≥65 years with no reported history of CHD, stroke or dementia, completed the 20-item Center for Epidemiologic Studies depression scale (CESD) questionnaire. First CHD and stroke events during follow-up were adjudicated by an independent expert committee. Hazard ratios (HRs) were estimated by Cox proportional hazard model. After a median follow-up of 5.3 years, 338 subjects had suffered a first non-fatal CHD or stroke event, and 82 had died from a CHD or stroke. After adjustment for study center, baseline socio-demographic characteristics, and conventional risk factors, depressive symptoms (CESD ≥ 16) were associated with fatal events only: fatal CHD plus stroke (HR = 2.50; 95% CI 1.57-3.97), fatal CHD alone (n = 57; HR = 2.21 ; 95%CI 1.27-3.87), and fatal stroke alone (n = 25; HR = 3.27; 95% CI 1.42-7.52). These associations were even stronger in depressed subjects receiving antidepressants (HR = 4.17; 95% CI 1.84-9.46) and in depressed subjects with impaired Instrumental Activities of Daily Living (HR = 8.93; 95% CI 4.60-17.34). By contrast, there was no significant association with non fatal events (HR for non-fatal CHD or stroke = 0.94; 95% CI 0.66-1.33). In non-institutionalized elderly subjects without overt CHD, stroke or dementia, depressive symptoms were selectively and robustly associated with first fatal CHD or stroke events.