Background: Treatment guideline ST segment elevation myocardial infarction (STEMI) has recommended opening the culprit infarct-related artery when primary coronary intervention (PCI) is required to patients (pts) with muti-vessel disease (MVD). The safety and efficacy of these two different PCI strategies of acute myocardial infarction (AMI) with MVD in the drug-eluting stent (DES) era are largely unknown. Methods: Study population is consisted of a total 1116 STEMI pts with MVD underwent primary PCI with DES enrolled in the Korean Acute Myocardial Infarction Registry (KAMIR) from Jan 2005 to Dec 2006. The pts were divided into two groups according to PCI strategy: Culprit-lesion revascularization group (Group 1, n=905) and Complete revascularization group (Group 2, n=215). In-hospital and 6-month clinical outcomes were compared between the two groups. Results: The baseline and angiographic characteristics were similar between the two groups except that history of coronary heart disease was more common in Group 1 (10.3% vs. 5.4%, P= 0.025). The procedural success rate and in-hospital mortality were similar between the two groups (0.4% vs. 1.4%, P=0.111, 91.5% vs. 92.1%, P=0.846, respectively). At 6-month follow up, the survival and freedom from MACEs was higher in Group 1 (864/901, 95.9% vs. 198/215, 92.1%, P=0.020) due to the incidence of TLR was higher in Group 2 (4.2% vs. 1.0%, P=0.001). Conclusion: Culprit-lesion revascularization strategy (infarct-related artery only) showed better midterm clinical outcomes compared with those of complete revascularization strategy in AMI pts with MVD requiring multivessel angioplasty in the DES era.