High heparin doses during cardiopulmonary bypass (CPB) have been suggested to reduce thrombin activation and consumption coagulopathy and consequently bleeding complications. The authors investigated the effect of a high heparin dose during CPB on point-of-care measurements of coagulation. The authors hypothesized that during CPB a high heparin dose compared with a lower heparin dose would reduce thrombin generation and platelet activation and tested whether this would be reflected in the results of rotational thromboelastometry (TEM) and platelet aggregation, measured with multiple electrode aggregometry (MEA). Prospective, randomized, controlled, open single-center study. University teaching hospital. Sixty-three consecutive patients undergoing elective coronary artery bypass grafting with CPB were enrolled. Patients were randomly assigned to receive either a high (600 IU/kg, n = 32) or a low (300 IU/kg, n = 31) initial dose of heparin. Target levels of activated clotting time during CPB were >600 seconds in the high heparin dose group and >400 seconds in the low heparin dose group. Blood samples were collected (1) preoperatively after induction of anesthesia, (2) 10 minutes after aortic declamping, (3) 30 minutes after protamine administration, and (4) 3 hours after protamine administration. TEM and MEA were then measured. There was no difference in blood loss up to 18 hours postoperatively (median 735 mL for high dose v 610 mL for low dose; p < 0.056) or transfusions between the groups. Total median heparin dose (54,300 IU v 27,000 IU; p = 0.001) and median antifactor Xa levels during CPB (9.38 U/mL v 5.04 U/mL; p = 0.001) were greater in the high than in the low heparin dose group. However, neither TEM nor MEA results differed significantly between the groups. Compared with a lower dose of heparin during CPB, a high dose of heparin had little effect on the point-of-care measurements of hemostasis, TEM, and MEA. Based on the similarity of platelet and coagulation activity assessments, the higher heparin dose does not appear to offer benefit during CPB. Copyright © 2020 Elsevier Inc. All rights reserved.