Background: RHD molecular analysis has been used to differentiate weak D and partial D. This discrimination can be of clinical importance because carriers of partial D antigen may develop anti-D when transfused with D-positive red blood cell units what is not commonly observed in the weak D phenotype, with rare exceptions. The aim of this study was to determine the type of D variants among Brazilian patients requiring chronic transfusions serologically typed as weak D. Methods: Samples from 87 patients (53 with sickle cell disease, 10 with thalassemia and 24 with myelodysplastic syndrome), typed as weak D by manual tube indirect antiglobulin test or gel test were first RHD genotyped by using the RHD BeadChip Kit (BioArray, Immucor). Sanger sequencing was performed when necessary. Results: RHD molecular analysis revealed 32 (36.8%) variant RHD alleles encoding weak D phenotypes and 55 (63.2%) alleles encoding partial D antigens. RHD variant alleles were present in the homozygous state or as a single RHD allele, one variant RHD allele associated with the RHD Y allele, or two different variant RHD alleles in compound heterozygosity with each other in 67 patients, 6 patients and 14 patients respectively. The most common RHD alleles predicting partial D were RHD*DAR1.2, RHD*DAR3.1, RHD*DAU4, RHD*DAU*6, RHD*DVI, RHD*DVII, RHD*DMH while the most common RHD alleles predicting weak D were RHD*weak D type 1, RHD*weak D type 3, RHD*weak D type 4.0 and RHD*weak D type 38. Alloanti-D was found in 9 (16.4%) cases with variant RHD alleles (specifically RHD*DAR1.2, RHD*DAR3.1, RHD*DVI and RHD*DVII) predicting a partial D. Conclusions: The frequency of partial D was higher than weak D in Brazilian patients serologically typed as weak D, showing the importance to differentiate weak D and partial D in chronically transfused patients to establish a transfusion policy recommendation. Systematic RHD molecular analysis in patients receiving red blood cell transfusions provides relevant information of variant RHD alleles improving transfusion therapy and preventing alloimmunization. It also helps to avoid wasting of D- red blood cell units because carriers with the most common weak D types may safely receive D+ units.