Thrombin generation is considered unavoidable during cardiac surgery using cardiopulmonary bypass (CPB). We compared the effects of open and closed circuits on coagulation and fibrinolysis under identical conditions of priming volume, heparin-coating, and anticoagulation and transfusion protocols. Thirty coronary surgery patients were randomized to surgery using open circuits with open reservoirs and cardiotomy suction (open group, n=15) or closed circuits without either (closed group, n=15). In the closed group, a cell-saving device was used instead of cardiotomy suction. Blood samples were collected at eight time points from before the operation to the first postoperative morning. Thrombin-antithrombin III (TAT), fibrinogen degradation products, and D-dimer were not elevated during CPB in the closed group, but were significantly increased in the open group (P<0.0001 for all markers). The peak TAT value at the termination of CPB in the open group was significantly correlated with CPB time (r(2)=0.879, P=0.037) and the simultaneous peak D-dimer value (r(2)=0.640, P=0.040). In conclusion, the use of closed circuits maximally suppressed thrombin generation and coagulofibrinolytic activation during coronary artery bypass grafting. The respective contribution of open reservoirs and cardiotomy suction to the perioperative thrombin generation remains to be elucidated.