Association between HLA-DRB1 alleles and rheumatoid arthritis (RA) has been known for more than three decades. However, the strength of these links varies between ethnic groups. This study examines the frequency of HLA-DRB1 alleles amongst Saudi RA patients. The DRB1 region of major histocompatibility complex was screened by polymerase chain reaction/sequence specific primers (PCR/SSP) in a total of 140 subjects including 70 RA patients and 70 matched healthy controls. HLA-DRB1 *04 was found to be the most frequent allele associated with RA followed by DRB1 *08 and DRB1 *10. On the other hand, the frequency of DRB1*06 was found to be decreased in RA patients as compared to controls. Molecular sub typing of the most prevalent allele DRB1 *04 revealed a statistically significant association between RA and DRB1 *0405. We conclude that an improved understanding about the influence of HLA on RA might help in predicting the susceptibility or protection against disease.