Background and Objectives: The supply of phenotyped red blood cells (RBC) for patients with several RBC antibodies presents a difficult task to hospital blood banks and regional blood centers. The aim of this study was to establish a low-cost typing system to allow extensive phenotyping of regular blood donors for clinically significant RBC antigens. Materials and Methods: We developed a new buffer that greatly intensifies the antigen-antibody reaction and thus reduces the quantity of serum needed for phenotyping. The procedure was carried out on microplates. Results: A total of 20,435 regular blood donors have been typed to date. For 752 units required for transfusion, 3,584 phenotyping tests were performed, validating the results by tube or gel typing methods; agreement was achieved in all cases. Conclusion: This technique seems adequate for phenotyping a large number of RBC units at very low cost, thus facilitating the availability of phenotyped blood.