Hypercholesterolemia is an important risk factor associated with myocardial infarction and ischemic stroke. Platelet hyperactivity has been described in hypercholesterolemia and cholesterol-lowering molecules (statins) are reported to reduce cardiovascular risk by way of either lipidic or non-lipidic actions (i.e. reduced platelet activity). The aim of our study was to evaluate the effect on platelet-dependent thrombin generation, as assessed according to Aronson, of diet and of tretament with statins. We studied 80 hypercholesterolemic subjects assigned to diet regimen and later treated with statins. Our data show an increased thrombin generation in hypercholesterolemic subjects with respect to normal controls. Diet was not able of reducing thrombin generation while simvastatin, cerivastatin and atorvastatin were able of reducing platelet activity regardless the grade of cholesterol reduction.