AIMS Although adjunctive cilostazol to dual antiplatelet therapy can reduce the risks of clinical events after percutaneous coronary intervention (PCI), whether genetic polymorphism can influence the pharmacodynamics of this regimen has not been evaluated. METHODS PCI-treated 127 patients taking triple antiplatelet therapy (���1 month) were enrolled. Platelet reactivity was assessed by conventional aggregometry and the VerifyNow P2Y12 assay. High on-treatment platelet reactivity (HPR) was defined as 5M ADP-induced maximal platelet reactivity (Aggmax) > 46%. CYP3A5*3, CYP2C19*2/*3, and ABCB1 3435C>T were genotyped. RESULTS CYP3A5*3 and ABCB1 3435C>T variants did not affect the antiplatelet effect of triple antiplatelet therapy. In order of non-carriers, one and two carriers of CYP2C19 loss-of-function (LOF) allele, Aggmax consecutively increased after the addition of 5 [24.6 짹 13.3% (95% confidence interval (CI), 20.8 to 28.5%) vs. 28.7 짹 12.2% (95% CI, 25.4 to 32.0%) vs. 32 짹 15.7% (95% CI, 25.8 to 38.7%), P = 0.062] and 20M ADP [34.2 짹 16.7% (95% CI, 29.3 to 39.0%) vs. 41.7 짹 14.2% (95% CI, 37.8 to 45.6%) vs. 44.9 짹 17.0% (95% CI, 37.9 to 51.9%), P = 0.007]. Likewise, late platelet reactivity and P2Y12 reaction units proportionally changed according to the number of CYP2C19 LOF allele. HPRs were observed in 9.2% of subjects: 6.3%, 7.4% and 20.0% in 0, 1 and 2 carriers of CYP2C19 LOF allele(s) (P = 0.099). In multivariate analysis, carriage of 2 CYP2C19 LOF alleles was a significant predictor for the prevalence of HPR (odds ratio 5.78, 95% CI 1.21 to 27.78, P = 0.028). CONCLUSION Among PCI-treated patients, the effect of triple antiplatelet therapy is influenced by the CYP2C19 LOF allele. Its clinical benefit needs to be validated according to the CYP2C19 metabolic phenotype in future clinical trials. [Adjunctive Cilostazol Versus High Maintenancedose ClopidogrEL in Acute Myocardial Infarction Patients According to CYP2C19 Polymorphism (ACCEL-AMI-2C19); NCT00915733; and Adjunctive Cilostazol Versus High Maintenance-dose Clopidogrel According to Cytochrome 2C19 Polymorphism (ACCEL-2C19); NCT01012193]. Keywords: platelet, clopidogrel, cilostazol, high on-treatment platelet reactivity, genetic polymorphism.