Background : Single nucleotide polymorphisms (SNPs) of Vitamin K epoxide reductase complex subunit 1 (VKORC1) affect warfarin dose response. Recently, some investigators reported that SNP (VKORC1 T2255C) has an association with arterial vascular disease (stroke, coronary artery disease and aortic dissection) through the regulation of coagulation cascade and vascular calcification. However, it is not well known whether this SNP affects the clinical outcome after percutaneous coronary intervention with drug-eluting stent (DES). Methods and Results : This is a prospective two-center clinical study, called as SeCaGene study. We prospectively collected genomic DNA from circulating monocytes in patients who underwent DES deployment from Sep 2003 to Dec 2006.. We compared clinical outcomes of patients after successful coronary angioplasty with DES according to their VKORC1 genotype. The primary end-point was a composite atherothrombotic events [death, myocardial infarction (MI), stent thrombosis and non-hemorrhagic stroke] after stent implantation. Mean follow-up duration was 602짹269 days. Genotyping was completed in 764 cases (62.3짹9.5yrs, 59.4% male and 27.8% diabetes mellitus). Genotype frequency TT vs non-TT was 83.8% vs 16.3%. This frequency was consistent with Hardy -Weinberg expectations. Baseline clinical characteristics between two groups were not different. During follow-up, patients with non-TT genotype showed more atherothrombotic events than TT group (7.3% vs, 2.7%, p=0.025) out of total twenty six atherothrombotic events [death(7), MI(11), stent thrombosis(4), stroke(4)]. In the multivariate analysis including clinical characteristics, non-TT genotype of VKORC gene was a significant predictor of atherothrombotic events (OR 3.12, 95% confidence interval 2.54~4.61,p=0.011). Conclusion : Patients who had non-TT genotype of VKORC1 gene, one out of six patients, showed poor clinical outcomes after drug-eluting stent implantation. VKORC1 SNP that is involved in coagulation system may be a good candidate of genetic predictors of atherothrombotic events in patients with atherosclerosis.