It is established that hormone therapy (HT) is related with significant increased prothrombotic risk factor. The aim of our study was to assess the effects of oral hormone therapy (o-HT) and transdermal hormone therapy (t-HT) on hemostasis parameters: fibrinogen (Fg) concentration, the maximum velocity of polymerization of clot formation, fibrin half-time lysis, plasma level of thrombin inhibitor of fibrinolysis (TAFI) and activity of generated thrombin and plasmin amidolytic activity. We observed that values of initial velocity of polymerization in o-HT group were increased (94.64 mOD/min vs. 131.50 mOD/min, p < 0.001) compared to control group. Fibrin lysis half-time increased in both groups with HT (controls - 18.26 min vs. 32.43 min (o-HT); 23.34 min transdermal hormone therapy (t-HT) p < 0.001) compared to controls. The activity of thrombin was statistically higher in plasma of women after o-HT (72.6 ± 8.5 mOD/min) than in patients with t-HT (53.7 ± 10.1 mOD/min) and controls (51.2 ± 10 mOD/min. Plasmin activity was the highest in controls (84.5 ± 10.2 mOD/min). The highest level of TAFI we observed in patients after oral hormones (80.38 ± 8.23%); women on transdermal HT had 61.58 ± 9.81% and the lowest concentration of TAFI we noted in controls 44.70 ± 10.16). The results of our study show that HT may partly explain the increase in venous thrombosis (VTE) and cardiovascular events reported after the use of it, especially the oral form of treatment.