Purpose: This study compared long-term safety and efficacy of sirolimus- (SES) versus paclitaxel-eluting stent (PES) implantation for the treatment of acute ST-elevation myocardial infarction (STEMI). Methods: A total of 308 consecutive patients were randomly treated with SES (n=154) or PES (n=154) in the setting of primary percutaneous coronary intervention for acute STEMI at three cardiac centers. Thirty-day and long-term (38짹12 months) clinical outcomes were assessed. Primary endpoint was incidence of stent thrombosis and major adverse cardiac events (MACE) including all cause mortality, myocardial infarction (MI), and ischemia-driven target lesion revascularization (TLR). We applied a classification of stent thrombosis set by the Academic Research Consortium (ARC). Results: The both group had similar clinical and angiographic characteristics. At 30 days, the rate of all cause mortality (2.6% for SES and 5.2% for PES, p=0.25) and MI (0% for SES and 1.3% for PES, p=0.50) were similar between two groups. Angiographic in-segment restenosis was significantly lower in SES over PES at 6-month (5.9% vs. 14.8%, p=0.03). During the 3-year follow-up, no significant differences were seen between two groups in terms of death (6.5% for SES and 10.4% for PES, p=0.219), MI (2.6% vs. 3.9%, p=0.750), TLR (3.9% vs. 8.4%, p=0.154) and MACE (12.3% vs. 18.8%, p=0.116). Overall cumulative incidence of stent thrombosis by any ARC criteria was gradually increased; 0.6% at 30 days, 0.6% at 1 year, 1.6% at 2 years, and 2.6% at 3 years. Late stent thrombosis (> 1 month) occurred in 1.9% for both SES and PES. The incidence of stent thrombosis was also similar in both groups during the 3-year follow-up (1.9% for SES versus 3.2% for PES, p=0.723). Conclusions: SES significantly outperformed PES in preventing angiographic restenosis in STEMI patients treated with primary angioplasty. However, long-term safety and efficacy evaluated by incidence of stent thrombosis and MACE were not different between two groups during the 3-year follow-up.