Background: Cytochrome P450 (CYP) 2C19 polymorphisms may cause interindividual and interethnic variation in the metabolism and disposition of its substrates. CYP2C19*2 and CYP2C19*3 are the most common polymorphisms, and show poor metabolic phenotypes. Recent data have shown that the CYP2C19*2 loss-of-function allele is associated with a marked decrease in platelet response to clopidogrel in acute coronary syndrome in Caucasians. However, It is unknown whether CYP2C19 *3, which is frequently noted in far east Asian, is also associated with platelet response to clopidogrel. Objectives: This study was conducted to analyze the effect of CYP2C19*2 and *3 polymorphisms on high post-treatment platelet reactivity (HPPR) on clopidogrel in Korean acute coronary syndrome patients, as a representative of far east Asian populations. Methods: The study included 136 consecutive patients undergoing percutanous coronary intervention (PCI). Adenosine diphosphate (ADP)-induced platelet aggregation by light transmittance aggregometry and the VerifyNow P2Y12 assay (Accumetrics Inc., USA) were assessed after a loading dose and after the maintenance dose of clopidogrel before discharge. CYP2C19 genotype was analyzed by snapshot method. Results: The genotypic distributions of CYP2C19*1/*1, *1/*2, *1/*3, *2/*2, and *2/*3 were 57 (41.9%), 47 (34.6%), 12 (8.8%), 14 (10.3%), and 6(4.4%), respectively. The frequencies of CYP2C19 mutant alleles in Korean were higher than Caucasians. The CYP2C19*2 and CYP2C19*3 polymorphisms were significantly associated with 5 關M, 20 關M ADP-induced maximal platelet aggregation, the platelet measures of VerifyNow P2Y12 assay (P<0.004). The CYP2C19*2 and *3 alleles were more frequent in clopidogrel hyporesonsiveness, defined by persistent HPPR (5 關M ADP-induced platelet aggregation >50%; P = 0.01). Conclusions: This study suggests that the CYPC19*2 and *3 alleles influence high-on clopidogrel platelet reactivity in far east Asian patients with acute coronary syndromes undergoing PCI. These findings can have a significant impact on the future design of pharmacogenetic antiplatelet treatment strategies for acute cononary syndrome patients.