The objective of this study was to investigate the difference between the closed circuit system and the open circuit system in clinical heparin-coated cardiopulmonary bypass (CPB) circuits with a centrifugal pump. We evaluated the coagulation, fibrinolysis, and inflammatory response in valvular heart surgery. Nineteen patients were assigned at random to a group for the closed circuit system or the open circuit system. This is the first report on the effect of a closed circuit in valvular surgery. We measured the platelet count, white blood cell count, plasma fibrinogen concentration, thrombin-antithrombin III complex, plasmin-Alpha2 plasmin inhibitor complex, D-dimer, interleukin-6, polymorphic neutrophil-elastase, and the plasma free hemoglobin. Blood samples were collected before the start of perfusion, 15 and 60 min after the start of perfusion, 60 min after the administration of protamine, and 1 day after the operation. During the perfusion, coagulation, fibrinolysis, and inflammatory responses were activated; however, no significant differences between the two groups were noted. In this clinical investigation with suction and the cell saving system, the closed circuit was not found to be superior to the open circuit with regard to biocompatibility.