This study evaluated the timing, causes, and predictors of death during long-term follow-up after primary angioplasty with stent implantation versus in-hospital fibrinolysis with a tissue plasminogen activator (alteplase). We randomized 1,572 patients with ST-elevation myocardial infarction to primary angioplasty or alteplase and followed them for 3 years. The causes of death were prospectively assessed by an end point committee unaware of the study treatment. A total of 225 patients (14.3%) died, 113 within the first 30 days and 112 between 31 days and 3 years. The mortality and causes of death did not differ between the 2 treatments. The causes of death were cardiogenic shock/congestive heart failure (41%), sudden death (17%), other cardiac death (10%), cancer (12%), and other noncardiac death (20%). Cardiac death was predominant during the first month only (86% of early deaths), and noncardiac death and cardiac death were equally frequent after 30 days (49% and 51% of late deaths, respectively). Independent predictors of death after discharge were age, left ventricular ejection fraction, diabetes, Killip class, and a lack of treatment with a beta blocker or statin. In conclusion, the causes of death did not differ between alteplase treatment and primary angioplasty with stent implantation. One half of the deaths within 3 years after ST-elevation myocardial infarction occurred during the first 30 days, and cardiac death was predominant during the first 30 days only.