RBC alloimmunization is a major complication associated with RBC transfusion in patients with SCD with serious complications for the patient including life-threatening delayed hemolytic transfusion reactions and an increase in the risks inherent to transfusion such as TRALI, infectious diseases and the hyperhemolysis syndrome. In addition, the presence of alloantibodies, which is often associated with the concomitant presence of autoantibodies, can lead to difficulty in finding compatible units, which can cause transfusion delays. The prevalence of alloimmunization vary according to the transfusion protocols used and may be reduced by matching for RBC antigens. Based on this, the aim of this study was to assess the prevalence of RBC alloimmunization in patients receiving transfusions with ABO and D matching, with phenotype matching for C, E and K antigens and with extended minor RBC antigen matching. A total of 368 patients with SCD, homozygous for HbS were enrolled. In this period, 81 patients received RBC units matched for ABO and RhD, 188 patients were matched for C, E and K and 99 patients were matched for ABO, Rh, K, Fya/Fy/b, Jka/Jkb and S/s antigens. Transfusion and antibody histories were obtained from our records, and antibody screening was done to assess the alloimmunization prevalence. Molecular typing was performed in all patients who had recent transfusions or a positive direct antiglobulin test by Laboratory Developed Tests (LDT) and HEA BeadChip (Immucor) to predict their antigen profile. RH variant alleles were determined in patient's antigen-positive who developed Rh antibodies using RHD and RHCE BeadChips (Immucor). Adsorption onto autologous RBC was also performed to aid the differentiation of autoantibodies from alloantibodies. Of the 368 patients evaluated, 128 were male and 240 female. Mean age was 37.4 years (range 18-60) and they received an average of 74 RBC units. Prevalence of alloimmunization in the SCD patients with ABO/RhD matched only units (n=81) was 54%. For individuals transfused with C, E and K matched units (n=188), alloimmunization prevalence was 13% and patients transfused with extended-matching units (n=99) the prevalence of alloimmunization was 0.8%. Antibody specificities developed by the patients receiving Rh and K matched units were: Anti-e, -D, -Jk a , -Jk b , -S, -Di a , -V and by the patients receiving extended matching were anti-C, -e, -V, -VS. The variant RHCE*ceS , RHCE*ceMO , RHD*DIIIa-CE(4-7)-D and RHD*DAU3 alleles were associated with the production of Rh antibodies in these patients and 9.8% of the alloimmunized patients developed autoantibodies. RBC alloimmunization rates shown to decrease to 24 % in patients with SCD transfused with RBCs matched for C, E and K antigens and to 1.5 % to patients with extended matching. Provision of RBC transfusions with limited and extended antigen matching is essential to reduce the rates of alloimmunization and hemolytic transfusion reactions in patients with SCD.