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Objectives: The purpose of this study was to compare long-term clinical outcomes after implantation of drug-eluting stents (DES) and bare-metal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI). Background: The evidence of long-term efficacy and safety after implantation of DES in patients with complex lesions is scarce. Methods: We randomly assigned 626 patients with STEMI referred within 12 h to have a DES or a BMS implanted in the infarct-related lesion with or without distal protection during primary percutaneous coronary intervention. Results: At 3 years, target lesion revascularization was 6.1% in the DES group compared with 16.3% in the BMS group (p < 0.001), and the rate of major adverse cardiac events was 11.5% versus 18.2%, respectively (p = 0.02). Whereas all-cause mortality did not differ significantly, the rate of cardiac death was higher in the DES group, 6.1% versus 1.9% for the BMS group (p = 0.01). The occurrence of reinfarction, stroke, and stent thrombosis was similar. Conclusions: Implantation of DES in patients with STEMI reduces the long-term rate of major adverse cardiac events compared with BMS, but patients with DES had a higher risk of cardiac death not attributed to myocardial infarction or stent thrombosis. (Drug Elution and Distal Protection During Percutaneous Coronary Intervention in ST Elevation Myocardial Infarction [DEDICATION]; NCT00192868) [ABSTRACT FROM AUTHOR]