Hormone therapy (HT) can be prothrombotic risk factor. We compared the effects of oral HT (o-HT) and transdermal HT (t-HT) on the kinetic of clot formation and fibrinolysis in postmenopausal women after 6 months HT using a multiparameter test. We observed that after HT, the level of fibrinogen was higher than in controls (Fg 3.12 g/l vs. 4.24 g/l (o-HT); 3,7 g/l (t-HT); p < 0.001) and values of velocity of polymerization in o-HT group were increased (95.84 mOD/min vs. 146.50 mOD/min, p < 0.001) compared to controls. Maximum absorbance of formed clots was higher in o-HT group (0.279 vs. 0.312, p < 0.001) than in controls, but in t-HT group was lowest (0.268). Fibrin lysis half-time increased in both HT groups (controls 17.16 min vs. 31.43 min (o-HT); 23.34 min (t-HT) p < 0.001) compared to values in controls. The results of our study show that o-HT caused the changes in clot formation and fibrinolysis than t-HT in postmenopausal women. The increased level of fibrinogen and its accelerated kinetics of polymerization as well as a lower rate of clot lysis may partly explain the increase in venous thrombosis and cardiovascular events reported after the use of HT, especially the oral form of that.