Blood group antigen immunogenicity is a crucial factor in red blood cell alloimmunization. Previous calculated estimates of immunogenicity suffered from several key shortcomings. To address these issues we have (1) introduced a correction factor for antibody persistence rates into traditional immunogenicity calculations, (2) calculated immunogenicities only in men to eliminate pregnancy-related antibodies, and (3) excluded antibodies reactive only at room temperature to minimize the contribution of naturally occurring antibodies. With these corrections, we have calculated the immunogenicities of common blood group antigens using data collected on clinically significant alloantibodies (n = 452) in a male patient population. We observed a 3- to 5-fold increase in immunogenicity for some antigens (ie, Jk(a), C(w), Lu(a)) and smaller changes in others compared with traditionally calculated estimates. In addition, we have calculated the transfusion-related immunogenicities of antigens traditionally associated with naturally occurring antibodies (eg, anti-Le(a), -Le(b), -M, and -P(1)).