Background The increasing use of fresh blood group O whole blood in acute trauma medicine makes it important to reevaluate the issue of hemolytic reactions related to the transfusion of ABO‐incompatible plasma. STUDY DESIGN AND METHODS This review summarizes and evaluates published articles and case reports concerning hemolytic reactions in connection with the transfusion of group O whole blood or blood products to nongroup O recipients. Results In 1945‐1986, 15 nonmilitary publications reported hemolytic transfusion reactions with group O blood/blood products. All patients recovered except for two fatalities. Late in World War II and during the Korean and Vietnam wars and onward in Iraq and Afghanistan only “low anti‐A, anti‐B titer” group O whole blood has been used as universal blood. In spite of a large number of units transfused, there are no reports of hemolytic reactions. Twenty‐five publications report hemolytic reactions after transfusion of group O platelets to nongroup O recipients. In all patients but one, the titer of the implicated A‐ or B‐antibody was >100 (saline) or >400 (antiglobulin) and all cases with an infused volume of incompatible plasma <200 mL were related to anti‐A or anti‐B antiglobulin titers >1000. Conclusion In emergency lifesaving resuscitation, the risk of hemolytic transfusion reactions from transfusion of group O blood to nongroup O recipients constitutes risk that is outweighed by the benefits. A low titer of anti‐A/B will minimize the risk for a hemolytic reaction, particularly if the screening is repeated after an immunization episode, e.g., blood transfusion, vaccination, or pregnancy.