Background: Rheumatoid arthritis (RA) is a chronic, progressive, inflammatory autoimmune disease that mainly targets the synovial membrane of the diarthroidal joints. The global prevalence of RA is estimated to be 0.24% and the prevalence rate is more in the female population (3:1) and increases with age. The major genetic risk factor for RA is conveyed by the human leukocyte antigen (HLA) genes. The HLA genes are highly polymorphic and differ between different populations, which influences the disease. Aims: To investigate whether an association exist between HLA alleles and RA among Omanis by determining, the frequency of HLA class I and II alleles among Omani RA patients and control groups, and the HLA allele(s) that is/are associated with RA and its parameters among the Omani population. Methods: - We included 102 RA patients fulfilling the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria and 104 individuals who are not affected by RA and/or any other autoimmune disease as controls. A total of 5 ml blood was collected from each individual. DNA was extracted and the HLA typing was performed using the Polymerase Chain Reaction Sequence Specific Primers (PCR-SSP) methodology. The Chi square test was used to investigate the significance of the associations. A p value <0.05 was considered significant. Results: HLA-B*15 (p=0.007), C*02 (p=0.001), DRB1*01 (p=0.039), DRB1*04 (p=0.004) and DRB4 (p=0.022) were associated with the susceptibility to RA. HLA-B*18 (p=0.005) and B*58 (p=0.002) were associated with protection against RA. We also observed associations in RA patients between different HLA alleles and different RA related parameters. Red blood cell (RBC) and platelet counts were associated with HLA B*40 and HLA-B*07 respectively, hemoglobin levels with HLA-A*74 and HLA DRB1*11. We observed association between erythrocyte sedimentation rate (ESR) and HLA-B*41, C+08 as well as DRB1*01, C-reactive protein (CRP) and HLA-B*41, C*17 as well as DQB1*01. The neutrophil count was associated with HLA-DRB1*12 and DQB1*03, lymphocyte count with HLA-A*24, B*23, C*08 and DQB1*04, monocyte count with HLA-A*33, C*04 and DRB1*10, and eosinophil count with HLA-DQB1*04. In addition, HLA-A*03, A*32, B*58 and DRB1*12 were found to be associated with WBC count. The levels of alkaline phosphatase (ALP) were found to be associated with HLA A*32, B*58 and C*03, while phosphate levels were associated with HLA-C*03. HLA C*04 and DRB1*04 were found to be associated with total calcium (total) levels and HLA A*01, A*02, B*53, C*16, DRB1*13, DQB1*03 and DQB1*05 were associated with albumin levels. Conclusion: We identified certain HLA Class I and I alleles that are associated with RA and its parameters among the Omani population. This confirms the involvement of both CD4+ and CD8+ T lymphocytes in the pathogenesis of RA and provide potential clues for a better management of RA in Omani patients.