Thrombin generation and subsequent fibrin deposition occur during cardiopulmonary bypass (CPB) using roller pumps (RPs) despite the administration of high dose heparin. The authors attempted to determine if less thrombin is generated and less fibrin is deposited during CPB using a centrifugal pump (CP). In Part 1 of the experiment, 12 pigs receiving 400 U/kg heparin underwent CPB, including hypothermia, cardioplegia, and aortic cross-clamping, using a CP or RP. Blood samples were collected throughout CPB to measure thrombin generation. At the end of CPB, the amount of fibrin deposited onto each filter was assessed spectrophotometrically. In Part 2, blood samples and arterial in-line filters were obtained from 20 patients undergoing CPB, using either RP or CP, and studied as described previously. The Part 1 results showed that thrombin generation and fibrin deposition in CP pigs were <50% of those seen in the RP pigs (p < 0.01 and p < 0.01, respectively). In Part 2, thrombin generation was significantly attenuated both during and after CPB in the CP patients (p < 0.01 and p < 0.01, respectively). However, there was no significant difference in fibrin deposition between the two types of pumps after their use in the patients undergoing cardiopulmonary bypass. It is concluded that there is less thrombin generation and subsequent fibrin deposition during CPB when using a CP instead of RP in a defined experimental in vivo situation, suggesting that there is less hypercoagulability during CPB when using a CP instead of an RP. However, a large study in more patients undergoing CPB for longer pump runs is required to determine the relevance of these observations on subsequent clinical endpoints.