Introduction: We aimed to investigate parameters for prediction of post-operative blood loss and re-operation in patients who underwent cardiopulmonary bypass. Methods: Thrombin generation assay, activated partial thromboplastin time, activated clotting time and rotational thromboelastometry (ROTEM) tests were performed at 4 time points in 65 patients: before skin incision (T1), after heparin injection (T2), after protamine reversal (T3) and before skin closure (T4). Results: Pre-operative endogenous thrombin potential (ETP) and peak thrombin levels were significantly lower in patients with high post-operative blood loss (≥ 800 mL) within 24 h than in those with low blood loss (< 800 mL). Clotting time (CT), maximal clotting firmness, clotting firmness time and alpha angle values of ROTEM measured at T2, T3 or T4 were significant predictors for high post-operative blood loss. An increase in CT-EXTEM over 4 time points was significant in patients who had a re-operation within 48 h compared to their counterparts. Conclusions: This study indicates that pre-operative ETP could predict high post-operative blood loss and that intra-operative ROTEM also helps to stratify risks of high post-operative blood loss and re-operation.