Membrane-dependent coagulation processes play a key role in acute coronary syndromes (ACS), where the generation of thrombin depends on the complex of activated factors X and V (prothrombinase complex) assembled on activated platelets. The aim of the present study was to evaluate prothrombinase activity in patients with ACS and to examine the effect of treatment with 80 mg/day atorvastatin on prothrombinase activity. Blood samples were obtained at admission from 22 patients with ACS, and then again at 2 weeks and at 16 weeks after double-blind randomization to either placebo or atorvastatin. Prothrombinase activity was evaluated by measuring the generation of thrombin by in vitro reconstructed thrombi, and also by measuring plasma levels of prothrombin fragment F1 + 2. Twenty age-matched subjects with stable angina and 11 without coronary disease were used as controls. At admission, prothrombinase activity and F1 + 2 were significantly higher in ACS patients than in controls. Prothrombinase activity was still high at 2 weeks while it returned to normal levels at 16 weeks. F1 + 2 remained high both at 2 and at 16 weeks. Our data indicate that prothrombinase activity is high in patients with ACS, and that it is not affected by high-dose atorvastatin.