- Background: Catastrophic life events are associated with the occurrence of cardiovascular incidents and worsening of the clinical course following such events. Objectives: To evaluate the characteristics and long-term prognosis of Holocaust survivors presenting with acute myocardial infarction (AMI) compared to non-Holocaust survivors. Methods: Israeli Jews who were born before 1941 and had been admitted to a tertiary medical center due to AMI during the period 2002–2012 were studied. Holocaust survivors were compared with non-Holocaust survivor controls using individual age matching. Results: Overall 305 age-matched pairs were followed for up to 10 years after AMI. We found a higher prevalence of depression (5.9% vs. 3.3%, P = 0.045) yet a similar rate of cardiovascular risk factors, non-cardiovascular co-morbidity, severity of coronary artery disease, and in-hospital complications in survivors compared to controls. Throughout the follow-up period, similar mortality rates (62.95% vs. 63.9%, P = 0.801) and reduced cumulative mortality (0.9 vs. 0.96, HR = 0.780, 95%CI 0.636–0.956, P = 0.016) were found among survivors compared to age-matched controls, respectively. However, in a multivariate analysis survival was not found to be an independent predictor of mortality, although some tendency towards reduced mortality was seen (AdjHR = 0.84, 95%CI 0.68–1.03, P = 0.094). Depression disorder was associated with a 77.9% increase in the risk for mortality. Conclusions: Holocaust survivors presenting with AMI were older and had a higher prevalence of depression than controls. No excessive, and possibly even mildly improved, risk of mortality was observed in survivors compared with controls presenting with AMI. Possibly, specific traits that are associated with surviving catastrophic events counter the excess risk of such events following AMI.