The importance of ABO blood group system compatibility in platelet transfusion is a subject of ongoing debate. Although there are theoretical advantages to pursuing a strict policy of providing exclusively ABO-compatible products, resource challenges may make this impractical for many transfusion services. Moreover, data supporting a net clinical benefit for this practice have been lacking. This presentation reviews ABO compatibility in the setting of platelet transfusion and examines the risks and benefits associated with transfusion practices allowing for platelet ABO incompatibility. Clinical cases illustrating complications associated with incompatible platelet transfusion will be presented.