Objectives : This study sought to determine whether the cytochrome P450 3A5 (CYP3A5) polymorphism is associated with clopidogrel resistance. Background : Clopidogrel resistance in some patients was suggested to be limitation of clopidogrel. Cytochrome P450 (CYP) 3A5 shares substrates with CYP3A4. The CYP3A5 gene polymorphism distinguishes an expressor (A,*1) and a nonexpressor (G,*3) allele. We hypothesized that CYP3A5 polymorphism is associated with clopidogrel resistance. Methods : First, we administered clopidogrel to normal volunteers with CYP3A5 nonexpressors (*3*3, n=5) and expressors (non-*3*3, n=5). Platelet aggregation test was performed at baseline, 4hr, 24hr and 6 days after clopidogrel administration. The same experiment was repeated with four days of itraconazole pretreatment. Second, we reviewed clinical outcomes of 353 patients treated with clopidogrel after successful coronary stenting according to CYP3A5 polymorphism. Results : Expressors have more platelet inhibition, especially when itraconazole was pretreated. (34 짹14 % vs. 9.8짹16 % at 4h (p=0.027), 36짹16% vs. 1.2짹10 % at 24hr (p=0.005)). After successful coronary stenting, cardiovascular events (death, stroke, myocardial infarction) ocurred more frequently in CYP3A5 nonexpressors (10/197) than in CYP3A5 expressors (1/156) within six months (p=0.026). In the multivariate analysis, genotype was still independent risk factor for cardiovascular events after coronary stenting. Conclusion : The CYP 3A5 polymorphism may be genetic background of interindividual variability in the response to clopidogrel and drug resistance.