The purpose of this study was to evaluate the behavior of the hemostatic system during treatment with gestodene-containing oral contraceptives in monophasic (SHD 356, n = 15) and triphasic (SHD 415, n = 15) formulations. No changes in platelet (beta-thromboglobulin, platelet aggregate ratio, and megathrombocyte) and routine clotting assays were observed. Factor VIIc/factor VIIag ratio and fibrinopeptide A values showed a significant (p less than 0.005) increase after three cycles of both treatments. A slight, significant increase (p less than 0.01) in antithrombin III activity was observed during triphasic treatment. Protein C was unchanged. Fibrinolytic activity and plasminogen levels were significantly increased (p less than 0.05 and p less than 0.001). After 6 and 9 months, the factor VIIc/factor VIIag ratio was still significantly enhanced, whereas fibrinopeptide A values significantly (p less than 0.05) decreased, even if they were higher (p less than 0.05) than basal values. The persistence of factor VII activation without enhanced thrombin formation after long-term use of oral contraceptives suggests that at that time the activity of antithrombotic mechanisms counteracts the prothrombotic tendency, thus helping to minimize unwanted side effects on hemostasis during long-term drug administration.