Osteoarthritis (OA) is a degenerative disease characterized by chronic inflammation of different joints in the body, which may lead to joint destruction and life disability. It is a complex disease of multifactorial etiology like genetic variation. Genetics is believed to be important in determining the susceptibility of OA. It was proven to be associated with histocompatibility locus antigen region. The aim of this study was to analyze of the frequencies of HLA-DQB1 alleles in OA Iraqi Arab Muslims. A cross–sectional case control comparative study included twenty six Iraqi Arab Muslims patients who had knee OA and admitted in the Orthopedic Department at Al-Kindy Teaching Hospital between September – 2012 to June – 2013, and compared to control ethnically matched group. HLA–DRQ1 genotyping was done by polymerase chain reaction-sequence-specific oligonucleotide probes (PCR-SSOP) method. There was an increased frequencies of HLA-DQB1*03:01:01 in patients with OA compared with healthy controls (P=0.0171, odds ratio=7.4118, 95% CI=1.4285-38.4564); also there were an increase in the HLA-DQB1* 02:01:01, HLA-DQB1* 0305 and *04 in patients with OA compared with the control group, but the differences were not statistically significant. Our results suggest a role of the HLA DQB1*03:01:01 system in the etiopathogenesis of OA.