Mean platelet volume (MPV) is an indicator of platelet activation. The present study was designed to investigate platelet function by measuring MPV, platelet count (PLC) and platelet mass (PLM) in prehypertensive (PHT) subjects. Additionally, we also evaluated the effects of lifestyle modification on platelet functions by measuring MPV, PLC and PLM. We selected 36 newly diagnosed PHT patients and 21 control subjects (BP < 120/80 mmHg) matched for age and sex. Lifestyle modifications (weight loss, reduced sodium intake, increased physical activity, limited alcohol consumption and the Dietary Approaches to Stop Hypertension (DASH) diet) were recommended to PHT individuals for 20 weeks. At entry into the study, although PLM and PLC values were similar between study groups, MPV values were significantly higher in the PHT group than in the control group (respectively, 10.41 +/- 0.93 fl vs. 9.56 +/- 1.04 fl, p < 0.01). Additionally, MPV was positively correlated with the systolic blood pressure (BP), body mass index (BMI) and insulin resistance (IR) in the PHT group (r: 0.41; p < 0.02, r: 0.37; p < 0.04, r: 0.35; p < 0.05, respectively). Only age and PHT were found to be independent predictors of MPV after regression analysis. The program substantially lowered BP (net reductions in systolic and diastolic BPs of 16.2 and 8.7 mmHg, p < 0.001, p < 0.001, respectively). In addition, BMI, waist circumference (WC) and IR were significantly reduced in the PHT group (p < 0.01, p < 0.01, p < 0.05, respectively). At the end of study, although PLM, PLC values were reduced in the PHT group, only the decrease in MPV reached statistical significance (respectively, 10.41 +/- 0.93 fl vs. 9.67 +/- 1.2 fl, p < 0.01). In closing, to our best notice, our study is the first to display a significant increase in MPV in PHT subjects and to show a decrease in MPV by lifestyle modification after 20 weeks. As a result, we consider that decreased platelet activation with multi-aspect effects of lifestyle modification therapy might play an important role in reducing thrombotic risk in PHT patients.