To evaluate the effect of transdermal estradiol therapy (ET) on coagulation and fibrinolysis markers in postmenopausal women.Prospective open trial study in 59 healthy hysterectomized postmenopausal women. Thirty women received transdermal ET (50 microg per day) during 3 months and 29 women formed the untreated arm.Baseline factor VII-tissue factor complex (VIIa-rTF), fibrinogen and plasminogen activator inhibitor-1 (PAI-1) levels decreased significantly (P < 0.01) after therapy. In contrast, tissue-type plasminogen activator antigen (t-PA) levels increased significantly (P < 0.01). After ET, there was no difference in protein C activity (PC), protein S activity (PS), plasminogen (PLG), and antithrombin III (ATIII) levels. None of participants reported thromboembolic events.ET elicited a decrement in blood biomarkers implicated in coagulation activation which in turn seemed to improve fibrinolytic activity. These results suggest that transdermal route does not impair thrombotic risk.