Background: Drug-eluting stent (DES) outperforms bare metal stent (BMS) in stable coronary artery disease. However, there are limited data comparing the long-term outcomes between DES and BMS in the treatment of acute ST-segment myocardial infarction (STEMI). Methods: We evaluated 684 unselected patients with STEMI who underwent percutaneous coronary intervention (PCI) at two centers in Korea from January 2003 to December 2006; 540 patients (78.9%) with DES and 144 (21.1%) with BMS. Patients were followed for the occurrence of target vessel failure (TVF): a composite of cardiac death, nonfatal myocardial infarction (MI) and target vessel revascularization (TVR). Results: The occurrence of TVF was significantly lower in DES group after a median follow-up of 26.0짹15.5 months (16.8% vs. 36.5%; HR, 0.37; 95% confidence interval CI, 0.24 to 0.60; P<0.001). The benefit of DES was mainly driven by a reduction in TVR (HR, 0.45; 95% CI, 0.29 to 0.72). Particularly DES was superior in the patients with multivessel disease (HR, 0.380; 95% CI, 0.26 to 0.57) and in those with small stent diameter (���3.0mm) (HR=0.34; 95% CI, 0.23 to 0.51). Analysis of propensity score-matched pairs also showed condordant results: a decreas in TVF (HR, 0.42; 95% CI, 0.25 to 0.71) and TVR (HR, 0.41; 95% CI, 0.21 to 0.80; P=0.009) in the DES group. With regard to safety concerns, overall incidence of stent thrombosis (ST) were comparable between the DES and BMS group (4.3% vs. 4.1%, P=0.748). Nevertheless, very late ST occurred in 3 patients (all DES group). On multivariate analysis, premature interruption of dual antiplatelet (DAT) within 6 months was shown to be associated with increased incidence of death and MI (HR, 7.19, 95% CI, 2.18 to 23.74). However, there was only a slight trend toward better outcome in the patients who recieved prolonged DAT over 12 months compared with those who were treated with DAT for duration of 6 to 12 months (HR, 0.51; 95% CI, 0.22 to1.19; P=0.118). Conclusions: DES exhibited superior mid- to long-term efficacy in unselected patients with STEMI, when compared with BMS, while showing comparable safety profiles.