The transfusion of ABO compatible but not ABO identical red blood cells and plasma and the transfusion of platelets and cryoprecipitate without concern for ABO in any manner, are practices that have been accepted as safe for patients. While these practices make managing blood component inventories easier by reducing component outdating, they do lead to the development of immune complexes, donor antibody induced hemolysis, and potentially endothelial cell and platelet injury. A growing body of evidence has shown that these practices are associated, likely causally, with negative consequences for patients including increased mortality. The adoption of a policy of providing only ABO identical blood components when practical, and avoiding infusion of ABO incompatible antibody, cellular and soluble antigen should thus become the optimal standard of care for patients.