The purpose of this study was to prospectively evaluate whether heparin and protamine doses administered using a standardized protocol based on body weight and activated clotting time values are associated with either transfusion of hemostatic blood products (HBPs) or excessive postoperative bleeding. Analysis using 10 multiple logistic or linear regression models in 487 cardiac surgical patients included perioperative variables that may have an association with either transfusion of HBP and/or excessive postoperative chest tube drainage (CTD). Prolonged duration of cardiopulmonary bypass (CPB), lower pre-CPB heparin dose, lower core body temperature in the intensive care unit, combined procedures, older age, repeat procedures, a larger volume of salvaged red cells reinfused intraoperatively and abnormal laboratory coagulation results (prothrombin time, activated partial thromboplastin time, and platelet count) after CPB were associated with both transfusion of HBP and increased CTD. Female gender, lower total heparin dose, preoperative aspirin use and the number of HBPs administered intraoperatively were associated only with increased CTD, whereas a larger total protamine dose was associated only with perioperative transfusion of HBPs. Preoperative use of warfarin or heparin was not associated with excessive blood loss of perioperative transfusion of HBPs. In contrast to previous studies using bovine heparin, data from the present study do not support the use of reduced doses of porcine heparin during CPB.