Background: Recent reports indicate that there are clopidogrel non-responders in the population. Clopidogrel is transformed to its active metabolite by cytochrome P450 3A. A single-nucleotide polymorphism (A6986G) in the CYP3A5 gene distinguishes an expressor (A) and a reduced-expressor (G) allele and largely predicts CYP3A5 content in liver and intestine. We postulate that clopidogrel resistance is associated with CYP3A5 polymorphism and investigated the relationship. Methods & Results: Patients (n=175) treated clopidogrel after stenting were investigated. We analyzed single nucleotide polymorphism (A6986G) by polymerase chain reaction (PCR) and restriction enzyme digestion. The genotype frequency was GG (97): AG (62): AA (16). The frequency of the GG genotype was 0.56, lower than that of Caucasians. But in nine patients who have developed major adverse cardiac events within 3months, the frequency of GG genotype was 0.89(GG: AG:AA=8:1:0). In the multivariate analysis including clinical and angiographic characteristics, the GG genotype was a significant predictor of early MACE(death, MI, stroke, SAT,TLR) after stenting (p=0.044). Follow up angiography was done at 6month (n=140). The GG genotype was not significant predictor of in-stent restenosis. In order to confirm the functional significance of the CYP3A5 polymorphism, we administered clopidogrel (300mg loading and 75mg qd for 7days) to nine normal volunteers of AA, AG, GG genotype (n=3 for each type). We performed platelet aggregation test (baseline, 4hr, 24hr and 7days). There were tendency that platelet aggregation was more inhibited in the AA type than non-AA type (AG+GG). Conclusion CYP 3A5 polymorphism seems to be associated with pharmacokinetics of clopidogrel and is associated with the early major adverse cardiac event after coronary stenting. This polymorphism may explain the individual difference in clopidogrel resistance.