Aim The red blood transfusion is a practice often used in patients with hematological and oncological diseases. However, the investigation of HLA system frequency in polytransfused patients is of great importance because multiple transfusions may lead to HLA alloimmunization, causing many complications and limitations for these patients especially in cases requiring organ or bone marrow transplantation. In view of the importance of HLA typing in these patients, the aim of this study was to investigate the allelic and haplotype frequencies from polytransfused patients from three different regions of Brazil. Methods Were analyzed HLA-A, -B, -C, -DRB1, -DQA1 and -DQB1 gene frequencies from 366 polytransfused patients of different regions from Brazil, which was divided onto three groups according to the region and ethnic (Group 1: Mixed population from the north of Paraná State (n=93), Group 2: Mixed population from the southeast of São Paulo State (n=96) and Group 3: Afro-Brazilian from the northeast of Brazil (n=177). The genotyping was analyzed by PCR-SSO, based on the Luminex technology (One Lambda®, CA, USA). Allelic and haplotypic frequencies of polytransfused patients for the three groups were performed using the Arlequin program. Results The most frequently allele frequencies observed were HLA-A∗02, A∗03, HLA-B∗15, B∗35, B∗51, HLA-C∗07, C∗04, C∗03, DRB1∗13, DRB1∗11, DRB1∗07, DRB1∗03, DRB1∗01, HLA-DQB1∗03, DQB1 02, DQB1∗06 and DQB1∗05 in all the three groups. When evaluating the differences between the groups for allelic variants, HLA- B∗57 (between group 1 and 2) and HLA- C∗12 (between group 1 and 3) were statistically different. The most frequently haplotypes found in the subjects were HLA-A∗01B∗08DRB1∗03, DRBI∗07DQB1∗02, DRB1∗01DQB1∗05, DRB1∗13DQB1∗06 and A∗02B∗35. Conclusion The HLA typing for polytransfused patients in each region has a great importance, as seen in this study; individuals from different regions from Brazil have HLA distribution not completely homogeneous.The insertion of a genotyping program for these patients would assist in the reduction of alloimmunization against HLA system in red blood transfusion with no leuko-depletion, thus avoiding further complications. C. Rodrigues:Grant/Research Support; Company/Organization; Immunogenetics Laboratory – UEM, FAPESP, CAPES, CNPq.