Allogeneic RBC exposure can induce alloantibodies capable of causing hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. Injection of polyclonal anti-RhD antibodies can inhibit anti-RhD alloantibody formation, preventing many of the negative consequences of RhD alloimmunization. Although polyclonal anti-RhD antibodies form the basis of RhD immunoprophylaxis, previous studies have sought to identify monoclonal antibody alternatives that similarly inhibit RBC alloimmunization. Unfortunately, monoclonal anti-RBC antibodies often fail to completely prevent RBC alloantibody formation. However, by combining 2 monoclonal antibodies that target distinct alloantigen epitopes, a monoclonal antibody cocktail can be generated with the same ability to prevent RBC alloimmunization as polyclonal antibody preparations. Ab, antibody; +, antibody formation; −, no antibody formation.