Platelet size, measured as the mean platelet volume (MPV), is associated with platelet reactivity. The MPV has been identified as an independent risk factor for future stroke and myocardial infarction. The aim of this study was to determine the association of MPV with the development of stoke or coronary artery disease (CAD) in diabetes mellitus (DM). The MPV was analyzed in 200 patients with DM (mean age, 66 years; 50.5% male). The primary endpoint was composite of ischemic stroke event /CAD. The mean MPV was 7.6짹0.8 fL. There were 14 incident stroke events and 8 CAD during a mean of 28.4 months of follow up. The Kaplan-Meier analysis revealed that the higher tertile MPV group (���7.9 fL) had a significantly higher stroke/CAD rate compared to the lower tertile MPV group (<7.3 fL) (29.9% vs. 3.9%, log-rank: P < 0.001). A higher MPV was an independent predictor of stroke/CAD risk after adjusting for age, sex, hypertension and hemoglobin A1c (HbA1c) level (hazard ratio: 9.96, 95% CI 2.29-43.33, P = 0.002) in the Cox proportional hazard analysis. When the MPV cut-off level was set to 7.95 fL using the receiver operating characteristic curve, the sensitivity was 91% and the specificity was 80% for differentiating between the group with stroke/CAD and the group without stroke/CAD. This value was more useful in patients with hypertension. Furthermore, DM patients with an MPV over 7.95 fL had high stroke risk without aspirin, especially in the hypertension group (Log-Rank < 0.0001). The results of this study show that the MPV was a predictive marker for stroke/CAD; its predictive power for stroke/CAD was independent of age, gender, hypertension and HbA1c in patients with DM. These findings suggest that antiplatelet therapy with aspirin may be needed in hypertension patients with a high MPV among patients with DM.