Pediatric patients, especially neonates and infants, undergoing cardiac surgery, are at particularly high risk for developing surgical bleeding. After separation from cardiopulmonary bypass (CPB), excessive bleeding in children frequently requires the administration of large volumes of blood products to achieve hemostasis. In the operating room (OR), this period of bleeding and transfusion of blood products is associated with hemodynamic instability, prolonged surgery time, hypothermia, and the need for escalating inotropic support. Bleeding frequently continues, preventing primary chest closure and often necessitating chest reexploration in the intensive care unit (ICU) or return to the OR. There are many reasons children undergoing cardiac surgery experience coagulopathy associated with large-volume blood transfusion. Some of the reasons include the heterogeneity of surgical operations, especially the surgical complexity in neonates and infants with immature coagulation systems, redo-sternotomies, cyanosis or single-ventricle anatomy, hypocalcemia, hypothermia, and acidosis. In addition, the CPB-associated inflammatory response, hemodilution, reduced oncotic pressure, platelet exhaustion, and consumptive coagulopathy with fibrinolysis also play roles in postoperative bleeding.