BACKGROUND High platelet reactivity during clopidogrel therapy has been linked to cardiovascular events after percutaneous coronary intervention (PCI). However, whether or not prognostic implications of residual platelet reactivity are same with different clinical spectrums is not well defined. METHODS A total of 2424 consecutive patients taking clopidogrel undergoing PCI with stent implantation had valid measurement of on-treatment platelet reactivity by VerifyNow P2Y12 assay. We determined the prognostic influence on clinical outcomes of high on-treatment platelet reactivity (HTPR) and its interaction according to clinical indications: acute coronary syndrome (n=1095) vs. stable angina (n=1329). The primary end point was defined as a composite of all-cause death, nonfatal myocardial infarction (MI), stent thrombosis, and stroke. RESULTS The mean follow-up duration was 2.2 years. In patients with acute coronary syndrome, the presence of HTPR was independently associated with higher risk of primary end point after adjustment of significant covariates (hazard ratio [HR] 1.92, 95% confidence interval [CI], 1.24-2.99; P=0.004). This association was consistent for patient with unstable angina/non-ST-elevation MI by a factor of 1.96 and those with ST-elevation MI by a factor of 2.05. However, in patients with stable angina, the presence of HTPR was not associated with the incidence of primary end point (HR 1.00, 95% CI, 0.72-1.39; P=0.98) (P=0.01 for interaction). CONCLUSION In patients receiving PCI with stent implantation and taking clopidogrel therapy, there was a significantly differential prognostic influence of on-site residual platelet reactivity on clinical outcomes between acute coronary syndrome and stable angina. Key words: C-reactive protein, drug-eluting stent, platelet function test.