Background Blood samples from patients with sickle cell disease (SCD) present to transfusion service with numerous antibodies, making the searching for compatible red blood cells (RBC) a challenge. To overcome this problem we developed an effective strategy to meet needs of supplying RBC-compatible units to SCD patients using DNA arrays. Methods We selected DNA samples from 144 SCD patients with multiple (receiving > 5 units) transfusions previously phenotyped for ABO, Rh(D, C, c, E, e), K1, Fy(a) and Jk(a). We also selected DNA samples from 948 Brazilian blood donors whose ABO/RhD phenotype matched that of the patients. All samples were analysed by DNA array analysis (HEA Beadchip(TM), Bioarray Solutions) to determine polymorphisms associated with antigen expression for 11 blood group systems (Rh, Kell, Kidd, Duffy, MNS, Dombrock, Lutheran, Landsteiner-Wiener, Diego, Colton, Scianna); and one mutation associated with haemoglobinopathies. Results Based on genotype results we were able to predict phenotype-compatible donors needed in order to provide compatible units to this group of patients. Based on their ABO/Rh phenotype we were able to find in this pool of donors compatible units for 134 SCD patients. Conclusion Blood group genotyping by DNA array contributes to the management of transfusions in SCD patients by facilitating the transfusion support with antigen-matched blood. It has the potential to improve the life of thousands of SCD-transfused patients by reducing mortality due to transfusion reactions and immunization.972147152