We compared the effects on hemostatic variables of transdermal estradiol and oral equine conjugated estrogens (CEE), both combined with medroxyprogesterone acetate, in 40 postmenopausal women, 22 randomly allocated to transdermal estradiol and 18 to CEE. Antithrombin III (AtIII), fibrinogen, factor VII, factor VIII and tissue plasminogen activator before and after venous stasis were measured at the start of therapy and after two and four months in all patients, and after 12 months in a subgroup of 21 patients (12 from the estradiol and nine from the CEE group). In the short-term study (two and four months), analysis of variance did not reveal any significant difference between treatments for any of the hemostatic variables. A significant treatment by time interaction was found only for fibrinogen levels: at two months they were significantly higher in the estradiol group. In the long-term study (12 months), a significant decrease in AtIII and a significant increase in factor VIII were observed in both groups, without differences between treatments. The clinical relevance of the observed changes is doubtful, but nevertheless they should be considered in a more extensive evaluation of the potential cardiovascular risk and benefits of hormone use.