© 2015 American Society for Histocompatibility and Immunogenetics. Objective: This study was performed to investigate the association between the HLA-DR series and rheumatoid arthritis (RA) in a Thai population. Methods: HLA-DR subtypes were determined in 100 Thai RA patients and 99 healthy controls (HC). HLA-DR typing was performed using INNO-LiPA HLA-DRB Decoder kits (Innogenetics) and reconfirmed using MICRO SSP HLA DNA Typing kits (One Lambda) for DRB1*02 and *04. Results: When compared with the HC, the RA patients had higher allele frequency (AF) of DRB1*04:05 (15.00% vs 7.07%, p=0.016, pc=NS, OR=2.319, 95%CI=1.189-4.522) and DRB1*10:01 (3.00% vs 0%, p=0.030, pc=NS), respectively. The DRB1*09:01 was slightly higher in the RA patients, without statistical significance. The AF of the shared epitope (SE) alleles (HLA-DRB1*01:01, *04:01, *04:05 and *10:01) was significantly higher in the RA patients (18.50% vs 7.58%, p=0.002, pc=0.046, OR=2.769, 95%CI=1.466-5.231, 99%CI=1.201-6.388). The AF of HLA-DRB4*01 also increased significantly more in the RA patients (40.50% vs 25.76%, p=0.002, pc=0.002, OR=1.962, 95%CI=1.282-3.003, 99%CI=1.121-3.433). The HLA-DRB3*03:01 was significantly lower in the RA patients (6.00% vs 14.14%, p=0.008, pc=0.023, OR=0.388, 95%CI=0.191-0.786, 99%CI=0.153-0.982). Conclusion: In the presence of SE, the DRB1*04:05 and HLA-DRB4*01 were associated with RA, and the DRB3*03:01 would be a protective allele against RA in a Thai population.