To assess the association of depression following myocardial infarction (MI) and cardiovascular prognosis. The authors performed a meta-analysis of references derived from MEDLINE, EMBASE, and PSYCINFO (1975-2003) combined with crossreferencing without language restrictions. The authors selected prospective studies that determined the association of depression with the cardiovascular outcome of MI patients, defined as mortality and cardiovascular events within 2 years from index MI. Depression had to be assessed within 3 months after MI using established psychiatric instruments. A quality assessment was performed. Twenty-two papers met the selection criteria. These studies described follow up (on average, 13.7 months) of 6367 MI patients (16 cohorts). Post-MI depression was significantly associated with all-cause mortality (odds ratio [OR], fixed 2.38; 95% confidence interval [CI], 1.76-3.22; p <.00001) and cardiac mortality (OR fixed, 2.59; 95% CI, 1.77-3.77; p <.00001). Depressive MI patients were also at risk for new cardiovascular events (OR random, 1.95; 95% CI, 1.33-2.85; p = .0006). Secondary analyses showed no significant effects of follow-up duration (0-6 months or longer) or assessment of depression (self-report questionnaire vs. interview). However, the year of data collection (before or after 1992) tended to influence the effect of depression on mortality (p = .08), with stronger associations found in the earlier studies (OR, 3.22; 95% CI, 2.14-4.86) compared with the later studies (OR, 2.01; 95% CI, 1.45-2.78). Post-MI depression is associated with a 2- to 2.5-fold increased risk of impaired cardiovascular outcome. The association of depression with cardiac mortality or all-cause mortality was more pronounced in the older studies (OR, 3.22 before 1992) than in the more recent studies (OR, 2.01 after 1992).