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Cardiopulmonary bypass (CPB) induces hemolysis and the activation of the inflammatory and coagulation systems. Several components of the CPB equipment may contribute to such phenomenon. We tested the effects of two differently designed centrifugal pumps (Bio-Pump, Medtronic and Revolution, Cobe) on several markers of hemolysis, coagulation, and inflammation: plasma free hemoglobin, prothrombin fragment 1.2, platelet factor 4, and P-selectin. Twenty patients requiring coronary artery bypass grafting were randomized to undergo CPB with one of the study centrifugal pumps, and 10 experiments (5 for each pump) were performed with a closed loop circuit to assess pumps’ performances over 6 circulation hours using human blood. CPB induced a significant elevation of all the tested markers. Neither in the in vivo nor in the in vitro study were significant differences observed between the groups. Because the Revolution centrifugal pump, which was recently designed and distributed, produced results comparable with those obtained with the Bio-Pump, it should be considered as safe as the Bio-Pump to perform clinical CPB.