As cardiac surgery volumes increase worldwide, major bleeding remains a significant complication following cardiopulmonary bypass (CPB) surgery. Accurate prediction of postoperative hemorrhage risk is crucial. This study aimed to establish optimal thromboelastography (TEG) parameter thresholds for predicting major postoperative hemorrhage in patients undergoing CPB during cardiac procedures, thereby creating a reliable early warning system to reduce hemorrhagic complications. This study retrospectively analyzed 3,810 cardiac surgery patients requiring CPB, divided into major bleeding, defined as 1,000 mL or more chest tube drainage within 24 hours (n = 245), and non-major bleeding (n = 3,565) groups. To identify independent risk factors, logistic regression analysis was used to compare the two groups. Then, the receiver operating characteristic (ROC) curves were developed to determine optimal predictive thresholds and evaluate sensitivity and specificity. The immediate postoperative coagulation index of −1.75 demonstrated a specificity of 60.0% (95% confidence interval [CI]: 58.4–61.7%) and sensitivity of 78.5% (95% CI: 73.3–83.8%) for predicting major bleeding following CPB surgery, with an odds ratio (OR) of 4.55 (95% CI: 3.24–6.38). Other immediate postoperative TEG parameters also showed predictive value, including reaction time (R; area under the curve [AUC] = 0.70), kinetics time (K) (AUC = 0.71), α-angle (AUC = 0.69), and maximum amplitude (MA; AUC = 0.67). Additionally, post-CPB MA of 58.05 mm also demonstrated predictive value for predicting postoperative major bleeding. TEG parameter analysis demonstrated that the immediate postoperative coagulation index provides high predictive accuracy for major postoperative hemorrhage in cardiac surgery patients undergoing CPB. Furthermore, other postoperative TEG parameters also demonstrate moderate predictive significance. These findings may help clinicians identify high-risk patients at an early stage and provide a reference for enhanced monitoring and clinical decision-making.