Introduction: Rheumatoid arthritis (RA) is known as a disease of obscure pathophysiology. Immunogenetic factors have always been found to be linked with the susceptibility and severity of Rheumatoid Arthritis (RA). Although polygenic interactions are reported in RA cases, however, strong associations of HLA class II genes with RA have been observed worldwide. Variations in disease progression, pathogenesis and associations with HLA class II alleles have been seen in different ethnic groups. Hence this study was taken up to analyze the frequency of DRB1 alleles in RA patients from the population of North Eastern India at tending Gauhati Medical College __ampersandsignamp; Hospital (GMCH). Aim: To investigate the frequency of DRB1 alleles in RA patients attending GMCH. Materials and Methods: The study was a case-control study where the case group consists of RA patients attending GMCH and the control group consists of healthy disease-free individuals. Blood samples from 150 cases (following ACR/ EULAR crite ria- 2010) and 150 controls were collected in EDTA vials after taking consent from the subjects using standard venipuncture pro cedure. DNA was extracted from each of the collected blood samples and DRB genotyping was done by the molecular method using SSP kits. Alleles were analyzed using kit specific Hit charts and appropriate software. Results: HLA allele status was evaluated in RA patients as well as the control group from the same geographical region. The frequency of HLA DRB1*10 was observed higher in the patient group compared to controls. (OR= 5.968, CI= 3.607 to 9.874, P__ampersandsignlt;0.01). The frequency of DRB5 was also found higher in the patient group, suggesting linkage with DRB1*10 and association with RA. The frequencies of DRB1*12 (OR= 0.126, CI= 0.054 to 0.291, P__ampersandsignlt;0.01), DRB1*14 (OR= 0.138, CI= 0.052 to 0.366, P__ampersandsignlt;0.01), DRB1*15 (OR= 0.615, CI= 0.389 to 0.972, P__ampersandsignlt;0.05) along with DRB3 (OR= 0.357, CI= 0.22 to 0.577, P__ampersandsignlt;0.01) were seen higher in controls compared to cases, suggesting a protective effect against RA in the study group. There was no statisti cal significance in the frequencies of HLA-DRB1 alleles viz. DRB1*01, DRB1*03, DRB1*04, DRB1*07, DRB1*08, DRB1*09 and DRB1*11 as observed in the study. Conclusion: The study suggests that HLA DRB1*10 allele is associated with the susceptibility to develop RA whereas DRB1*12, DRB1*14, DRB1*15 are having a protective effect on RA in the study population.