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Abstract: Introduction: Rheumatoid arthritis (RA) is a chronic, systemic and autoimmune disease affecting 0.5–1% of the world population. Genetic and environmental factors are already established as being involved in the development of RA. Different human leukocyte antigen (HLA)‐DRB1 alleles have major pathogenic effects to the development of RA. Objective: To determine the HLA‐DRB1 allelic frequency of RA in one Bangladeshi tertiary care center. Methods: This case–control study was conducted at the Microbiology and Rheumatology Department of Bangabandhu Sheikh Mujib Medical University (BSMMU). Fifty‐two patients diagnosed as having RA and 52 healthy controls were enrolled. Buccal swabs were collected from all subjects and HLA‐DRB1 typing was carried out with polymerase chain reaction with sequence‐specific primers (PCR‐SSP) of low resolution. Blood was also collected for auto‐antibodies (rheumatoid factor [RF] and anti‐cyclic citrullinated peptide [anti‐CCP]) detection from all subjects. RF was detected by nephelometry and anti‐CCP was detected by using the enzyme‐linked immunosorbent assay method. Statistical associations of HLA antigen between the groups were determined by chi‐square test. Results: In RA patients DR*04 and DR*10 were found at the DRB1 locus at higher frequencies (20.5%, P = 0.0035 and 18.3%, P = 0.0045, respectively). However, the frequency of DR*15 was significantly lower (P = 0.005) in RA cases (18.3%) than the control group (35.6%). The frequencies of autoantibodies (anti‐CCP and RF) were compared between approximate shared epitope (SE) positive and SE negative patients, and no significant association was found. Conclusions: In this study DRB1*04 and DRB1*10 alleles were significantly associated with RA patients while DRB1*15 was found more in the control group. [ABSTRACT FROM AUTHOR]