In view of the improved care of thalassemic patients which resulted in doubling of life expectancy, additional previously undescribed complications are now being recognized.In particular, a chronic hypercoagulable state has been observed in these patients, yet the actual mechanism of its production has not been fully elucidated. To our knowledge, the tissue factor pathway and its inhibitor have not been studied in thalassemics. The aim of the present work was to estimate tissue factor pathway inhibitor (TFPI) relation to oxidative stress assessed by thiobarbituric acid reactive substances (TBARS). Twenty patients with thalassemia major and ten healthy controls were enrolled in the study. Complete blood picture, serum ferritin, screening tests for coagulation, prothrombin and partial thromboplastin times(PT,PTT) and prothrombin activity (P activity %) have been estimated. The mean TFPI was higher in patients than controls but did not reach statistical significance, TBARS and serum ferritin were significantly higher in patients than controls(p=0.000)reflecting the presence of oxidative stress. No relation was found between TFPI and chelating agent (desferrioxamine) intake, splenectomy or TBARS. In conclusion, tissue factor pathway (TFP) as reflected by increased TFPI could be, at least in part incriminated in the thalassemia-induced hypercoagulable state.