Polycythemia vera (PV) is a clonal myeloproliferative disorder characterized by predominantly excessive erythrocyte production. During the course of the disease, bleeding or thrombosis may be observed. In PV patients, the influence of antifibrinolytic activities on development of thrombohemorrhagic complications remains to be elucidated. In the present study, alterations in antifibrinolytic activity of PV patients and the effects of treatments on these alterations were investigated. Newly diagnosed and therapy-naive 22 PV patients were included. Thrombomodulin (TM), plasmin-alpha 2-antiplasmin complex (PAP), plasminogen activator inhibitor-1 (PAI-1) and thrombin activable fibrinolysis inhibitor antigen (TAFIa) levels were measured in all individuals and after phlebotomy and 5-hydroxyurea (5-HU) therapy in PV patients. TM, PAP, PAI-1 and TAFIa values of the patient group were higher than those of the controls. After phlebotomy, no changes were detected in TM, PAI-1 and TAFIa values, but PAP values decreased. On the contrary, 5-HU treatment resulted in a marked decrease in TM, PAI-1, PAP and TAFIa levels. These findings suggested that the changes in antifibrinolytic activity and endothelial dysfunction might be contributed to formation of intravascular thrombosis in PV patients, even though not clinically overt. 5-HU in addition to phlebotomy affects antifibrinolytic activity and may have an influence on diminishing predisposition of thrombosis.