Summary. Background: Bleeding after cardiopulmonary bypass (CPB) is a major cause of morbidity and mortality and consumes large amounts of blood. Identifying patients at increased risk of bleeding secondary to hemostatic impairment may improve clinical outcomes by allowing early intervention. Methods: This present study recruited 77 patients undergoing CPB and measured coagulation screens, coagulation factors, TEG®, Rotem® and thrombin generation (TG) before surgery and 30 min after heparin reversal. The tests were analyzed to investigate whether they identified patients at increased risk of excess bleeding (defined as > 1000 mL) in the first 24 h postoperatively. Results: Patients who bled > 1000 mL had a lower: platelet count (P < 0.02), factors (F)IX, X and XI (P < 0.005), endogenous thrombin potential (ETP) and an initial rate of TG (P < 0.02) and higher activated partial thromboplastin time (aPTT) (P < 0.001) than patients who bled < 1000 mL. Receiver operating characteristic (ROC) analysis was significant for post-operative TG and aPTT (P < 0.001). Furthermore, reduced pre-operative TG was associated with increased postoperative bleeding (P < 0.02). Pre- and postoperative TG were correlated (ρ = 0.7, P < 0.001). TEG®, Rotem® and prothrombin time (PT) at either time point were not associated with increased bleeding. Conclusion: These data suggest that pre-operative defects in the propagation phase of hemostasis are exacerbated during CPB, contributing to bleeding post-CPB. TG taken both pre- and postoperatively could potentially be used to identify patients at an increased risk of bleeding post-CPB.