Background: Acute coronary syndromes, characterized by the rupture of unstable plaque and the subsequent thrombotic process involving platelets, have been increasing in relative frequency. The central role of platelet activation has long been noticed in this pathophysiology; hence, many therapies have been directed against it. In this study, we have aimed to search prospectively the value of mean platelet volume (MPV), which is a simple and accurate measure of the functional status of platelets, in patients hospitalized with diagnosis of acute coronary syndromes (ACS). Materials and methods: A total of 216 consecutive patients (156 male, 60 female) hospitalized with the diagnosis of non-ST segment elevation (NSTE) ACS within the first 24 h of their chest pain were enrolled. One hundred and twenty patients, matched according to sex and age, with stable coronary heart disease (CHD) (85 male, 35 female) were enrolled as a control group. Patients were classified into two group: those with unstable angina (USAP, n = 105) and those with non-ST segment elevation myocardial infarction (NSTEMI, n = 111). Results: MPVs were 10.4 +/- 0.6 fL, 10 +/- 0.7 fL, 8.9 +/- 0.7 fL consecutively for NSTEMI, USAP and stable CHD with significant differences. Patients with ischemic attacks in the first day of hospitalization accompanied by > 0.05 mV ST segment shift had significantly higher MPV compared to those without such attacks (P = 0.001). Multivariable logistic regression analysis yielded that MPV (P = 0.016), platelet count (P < 0.001), and the presence of > 0.05 mV ST segment depression at admission (P = 0.002) were independent predictors of development of NSTEMI in patients presenting with NSTE ACS. Conclusion: In patients presenting with NSTE ACS, higher MPV, though there are overlaps among subgroups, indicates not only more risk of having NSTEMI but also ischemic complications.