The exposure of blood to foreign surfaces during extracorporeal circulation (ECC) leads to an activation of the coagulation system. In arteriosclerotic patients thrombin activation is increased and plasma fibrinogen is elevated, while protein C levels are reduced. In this study we investigated the influence of different cardiac diseases on ECC-induced thrombin generation and activation of the thrombomodulin-protein C system. Twenty-four patients undergoing either elective coronary artery bypass grafting (CABG) or elective aortic valve replacement (AVR) were included in the study. Blood samples were taken at different time intervals before, during and after ECC, and in the postoperative period. Plasma concentrations of thrombin-antithrombin III-complex (TAT), modified antithrombin (ATM), prothrombin fragment F1+2, free protein S, thrombomodulin, and protein C-antigen were determined by ELISA. Fibrinogen and antithrombin III levels were detected by nephelometry. Both groups were comparable with respect to biometric and ECC-related data. TAT concentrations were elevated in both groups after induction and increased during surgery (p<0.001). As a marker of thrombin generation levels of F1+2 were higher in the CABG group during cardiopulmonary bypass (p=0.003). In CABG patients ATM peaks were higher during ECC (p=0.0024). Significantly higher plasma thrombomodulin concentrations were found in CABG patients after induction (p<0.001), while protein S concentrations were higher in the AVR group (p=0.002). Protein C levels and antithrombin III concentrations did not differ between the groups. Patients undergoing CABG were found to have lower protein S levels and increased plasma thrombomodulin concentrations as markers of endothelial damage. In these patients contact activation and as a consequence thrombin generation takes place at a higher level, indicating a hypercoagulable state. Thromboembolic events in the perioperative period may be caused by different hemostatic changes in CABG patients.