Background: To compare long-term (3-year) safety and efficacy of paclitaxel eluting stents (PES) versus sirolimus eluting stents (SES) for the treatment of acute ST elevation myocardial infarction. Methods: The 549 consecutive patients were treated with PES (n=187) or SES (n=362) in the setting of primary percutaneous coronary intervention for acute myocardial infarction in this multicenter registry. Thirty-day and long-term clinical outcomes (2810 months) were clinically assessed. Primary endpoint is incidence of stent thrombosis and major adverse cardiac events (MACE) including all cause mortality, myocardial infarction (MI), and target lesion revasularization (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 (4.3% for PES and 4.1% for SES, p = 0.941) and MI (2.1% for PES and 1.4% for SES, p =0.498) was similar between groups. Angiographic restenosis was significantly lower in SES (6.0%) and PES (14.4%, p=0.006). During the 3-year follow-up, no significant differences were seen between groups in terms of death (7.9% for PES and 6.5% for SES, p = 0.893), MI (3.9% vs. 3.4%, p = 0.562), TLR (8.3% vs. 6.4%, p = 0.318) and MACE (15.9% vs. 12.8%, HR 1.24; 95% CI, 0.72-2.13; p=0.441). Stent thrombosis (overall cumulative incidence; 1.9% at 30 days, 2.4% at 1 year, 2.6% at 2 years, and 3.3% at 3 years) occurred in 2.8% for PES versus 3.6% for SES during the 3-year follow-up (HR 0.95; 95% CI, 0.29-3.10; p=0.788). Late stent thrombosis (> 1 month) occurred in 0.6% for PES versus 2.2% for SES (p=0.259). Conclusions: Despite significant reduction of angiographic restenosis in SES versus PES, no differences were seen in MACE and incidence of stent thrombosis between PES and SES for the treatment of acute myocardial infarction during 3-year follow-up.