This prospective, randomized, controlled study evaluated the effect on acute immunologic transfusion reactions and transfusion efficacy when major crossmatching was performed prior to transfusion in transfusion-naïve anemic cats. Transfusion efficacy was based on the packed cell volume increase from baseline per mL/kg of packed RBCs transfused. Forty-eight cats were randomized into either the study group (ie, receiving crossmatch and blood type compatible packed RBCs) or the control group (ie, receiving noncrossmatched blood type compatible packed RBCs). No significant differences in incidence of transfusion reactions or transfusion efficacy between the groups was noted. The authors concluded that the results do not support use of major crossmatch testing to increase efficacy of and decrease adverse events associated with RBC transfusion in AB blood typed transfusion-naïve cats.