Disseminated intravascular coagulation frequently occurs after global ischemia and reperfusion due to cardiac arrest. The present study was performed to demonstrate the role of tissue factor for coagulation pathway activation, as well as to investigate the precise time course of tissue factor pathway inhibitor (TFPI) during and after cardiopulmonary resuscitation (CPR). Thirty-two of out-of-hospital cardiac arrest patients were classified into two groups, those who achieved return of spontaneous circulation (ROSC) n=13 and those without ROSC n=19. Ten normal healthy volunteers served as control subjects. Serial levels of tissue factor and TFPI were measured during and after cardiac arrest and CPR. In patients with ROSC, cardiac arrest and CPR led to persistent increases in the levels of tissue factor that peaked 6 hours after arrival at the Emergency Department. Tissue factor levels in patients without ROSC also showed marked elevations compared to those of the control subjects. In both groups, the levels of TFPI were significantly lower than those in the control subjects. However, we could not find differences in the levels of the two markers between the patients with ROSC and those without ROSC. In conclusion, we demonstrated persistent elevation of the tissue factor levels associated with low TFPI during and after CPR in patients with out-of-hospital cardiac arrest. These results indicate the activation of the extrinsic coagulation pathway without adequate TFPI generation, which may contribute to thrombin activation and fibrin formation after whole-body ischemia and reperfusion.