Objectives: To assess the switch effect of non-CYP3A4-metabolized statin on platelet reactivity (PR) among patients receiving clopidogrel and atorvastatin coadministration. Background: Because CYP3A4 enzyme contributes to clopidogrel metabolism, CYP3A4-metabolized statin can affect the antiplatelet effect of clopidogrel. Methods We enrolled 50 patients with increased PR [20關M ADP-induced maximal platelet aggregation (MPA)>50%] during chronic administration of atorvastatin (10mg/d) and clopidogrel (75mg/d) (���6 months) after percutaneous coronary intervention (PCI). They were randomly assigned to change atorvastatin to either rosuvastatin 10 mg/d (n=25) or pravastatin 20 mg/d (n=25). PR was assessed before and after 15-day switch therapy by conventional aggregometry and VerifyNow. Primary endpoint was a change of 20關M ADP-induced MPA before and after switch. High on-treatment platelet reactivity (HPR) was defined as 5關M ADP-induced MPA>46% or P2Y12 reaction units (PRU)>235. Results: All patients completed the study without specific events. Absolute changes of 20 and 5關M ADP-induced MPAs were significant after switch [66.9짹8.4% to 60.3짹15.0%; 95% confidence interval (CI), 3.2~10.1%; p<0.001 and 52.7짹10.7% to 46.4짹16.7%; 95% CI, 2.5~10.2%; p<0.001, respectively). Likewise, the results of VerifyNow significantly changed after switch (p���0.001). After switch, the prevalence of HPR was significantly decreased (16~32%). This pharmacodynamic effect was similar after rosuvastatin or pravastatin administration. Change of 20關M ADP-induced MPA was influenced by functional variability of ABCB1 C3435T and CYP genes. Conclusions: Among PCI-treated patients with increased platelet reactivity during clopidogrel and atorvastatin coadministration, the switch to non-CYP3A4-metabolized statin can significantly decrease platelet reactivity and the prevalence of HPR. This switch effect appears similar irrespective of the type of non-CYP3A4-metabolized statin.