Group O RBCs are typically issued for urgent transfusions to avoid ABO-incompatible hemolytic transfusion reactions (HTRs). Identification of other clinically significant alloantibodies requires an antibody detection test, and emergency release (ER) of RBCs before its completion carries a risk of non-ABO alloantibody-mediated HTRs. We performed a retrospective review of 1,002 ER RBC transfusions involving 265 ER episodes (262 recipients) in a tertiary medical center, 2006-2008, to determine the risk of non-ABO alloantibody-mediated HTRs. A positive antibody detection test was found in 29 (10.9%) of 265 ER episodes, with clinically significant alloantibodies in 17 (6.4%) of 265 ER episodes. Fifteen antigen-incompatible RBC units were transfused to 7 recipients with clinically significant alloantibodies; 1 transfusion was followed by an HTR. Based on our study, transfusion of ER RBCs before completion of routine blood bank testing carries a low risk of non-ABO alloantibody-mediated HTRs (1/265 [0.4% ER episodes]) and receipt of antigen-incompatible RBCs (7/265 [2.6% ER episodes]).