The authors aimed to evaluate the influence of transdermal hormone therapy (HT) in the blood coagulation parameters. Fifty-eight postmenopausal women received: G1-transdermal estradiol (E2) (50 mg), G2-E2+oral micronized progesterone (100 mg/day), and G3- E2+oral medroxyprogesterone acetate (2.5 mg/day) for six months. Statistical relevance was seen mainly in G1 and G2. G1 showed a decrease in prothrombin time (PT), fibrinogen (FG), and thrombin time (TT) at six months (p < 0.05) compared to baseline values. G2 showed an increase of PT (p < 0.05) and a reduction of activated partial thromboplastin time (aPTT), AT III at three months (p < 0.01). AT III showed an increase after six months (p < 0.05), as well as F1+2 (p < 0.05). G3 exhibited a decrease of PT after three and six months of transdermal HT. Data suggests that E2 alone or E2+OMP are correlated with some variations of anticoagulant and procoagulant factors. E2+MPA avoids any major activation of blood coagulation in patients who receive transdermal HT.