Earlier reports of associations between panic disorder, depression, and ischemic heart disease have not evaluated the role of the drugs used to treat these conditions. As part of a larger study on reducing cardiovascular disease in an entire community, we estimated the association between psychotropic drugs and ischemic heart disease in a large community-based population using a cohort study design. We defined exposure as current use of psychotropic medications at the time of the health interview. We determined ischemic heart disease by International Classification of Diseases, 9th revision, Clinical Modification, codes and by an epidemiologic algorithm using clinical diagnostic criteria. An elevated risk for clinically significant ischemic cardiac events was moderately associated with benzodiazepine use [relative risk (RR) = 2.0; 90% confidence interval (CI) = 1.1–3.9] and strongly associated with antidepressant use (RR = 5.7; 90% CI = 2.6–12.8), although the latter estimate was based on only six antidepressant users who had an ischemic event.