Clopidogrel therapy is the standard of care in patients with acute coronary syndrome (ACS) and stent implantation. However, concern arises because 25% of subjects are nonresponders to clopidogrel. As this nonresponsiveness is associated with increased adverse outcome, detection of these subjects in daily practice is important in order to withhold a more aggressive therapy and closer follow up. In this study we aimed to evaluate the relation between mean platelet volume (MPV) which is an indicator of platelet activation and clopidogrel nonresponsiveness.The study was planned as a prospective cohort study. A total of 185 patients who had been on clopidogrel therapy for any acute coronary syndrome were enrolled in this study. Clopidogrel responsiveness was analyzed by Multiplate MP-0120 device by using the method of whole blood aggregometry. Blood samples were drawn 3.5 days after clopidogrel loading dose. The amount of ADP induced platelet aggregation was assessed as area under curve (AUC), and a cut-off value of 500, above which the patient is considered as clopidogrel nonresponder, was used. MPV was analyzed from the blood which were sampled at the admission of the patient by using automatic hemocounter. Independent sample t-test, ROC analyses and logistic regression analsis were used in statistical analysis.Among the 185 patients analyzed 41 were found to be clopidogrel nonresponder (22.1%). Mean MPV was found to be significantly higher in nonresponders compared to responders (8.7±0.82 fL vs. 8.1±0.83 fL, p<0.001). A cut-off value of 8.3 fL for MPV was detected in prediction of clopidogrel nonresponsiveness with a sensitivity of 76.6% and specificity of 68.3% (OR: 6.4; 95% CI 2.9-14.1, AUC: 0.70, p<0.001).This study showed that MPV can be used as a predictor of clopidogrel resistance in patients with ACS.