Although patients with impaired glucose tolerance (IGT) are at increased atherothrombotic risk, it is unclear how antiplatelet drugs act in patients with IGT. The aim of this study was to investigate the pharmacodynamic response to clopidogrel in patients with IGT and insulin resistance (IR). A 75 g oral glucose tolerance test was performed in 65 coronary artery disease (CAD) patients on aspirin and clopidogrel therapy. Platelet function tests were assessed at 3 time-points by light transmittance aggregometry using ADP (5 and 20 μmol/L) stimuli. 30 patients had IGT and 35 normal glucose tolerance (NGT). Among them, 13 patients showed IR. Following ADP stimuli, patients with IGT showed significantly higher maximal platelet aggregation at each time point than those with NGT patients. This resulted in greater high on-treatment platelet reactivity (HPR) rates at each time point in IGT patients (53.3-36.7 vs. 14.3-11.4 %, p < 0.05). A multivariable logistic regression analysis showed that IGT status was the strongest predictor of HPR (odds ratio 7.54, 95 % CI 1.95-29.1, p = 0.003). Following a glucose load, profiles of platelet reactivity varied according to IR status, with minimal changes over time in patients with IR, while there was a significant reduction in the non-IR patients. In aspirin and clopidogrel-treated patients with CAD, IGT is associated with enhanced platelet reactivity and increased rates of HPR compared with NGT patients. These findings suggest the presence of platelet dysfunction in patients with IGT, which may be attributed to the presence of IR.