Background This study evaluated the prognostic significance of a novel bleeding severity classification in adult patients undergoing cardiac operations. Methods The European multicenter study on Coronary Artery Bypass Grafting (E-CABG) bleeding severity classification proposes 4 grades of postoperative bleeding: grade 0, no need of blood products with the exception of 1 unit of red blood cells (RBCs); grade 1, transfusion of platelets, plasma, or 2 to 4 units of RBCs, or both; grade 2, transfusion of 5 to 10 units of RBCs or reoperation for bleeding, or both; grade 3, transfusion of more than 10 units of RBCs. This classification was tested in a cohort of 7,491 patients undergoing CABG or valve operations, or combined procedures. Results The E-CABG bleeding severity grading method was an independent predictor of in-hospital death, stroke, acute kidney injury, renal replacement therapy, deep sternal wound infection, atrial fibrillation, intensive care unit stay of 5 days or more, and composite adverse events of death, stroke, renal replacement therapy, and intensive care unit stay of 5 days or more. The area under the receiver operating characteristic curve of the E-CABG bleeding severity grading method for predicting in-hospital death was 0.858 (95% confidence interval, 0.827 to 0.889). E-CABG bleeding severity grades 0 to 3 were associated with in-hospital mortality rates of 0.2%, 1.1%, 7.9%, and 29.0%, respectively (p