Background/Aim: The inflammatory disorder rheumatoid arthritis (RA) affects quality of life and worsens with symptoms in the extra-articular tissues and systemic joints. The most significant member of the Cytochrome P450 enzyme family, Cytochrome P450 2C9 (CYP2C9), plays an essential role in the alkylation, demethylation, and hydroxylation of a variety of substances. Insufficient studies as to whether the susceptibility to rheumatoid arthritis is genetic exists. Therefore, our study presents new information on whether CYPC9 is a genetic risk factor. In this study, we sought to determine whether rheumatoid arthritis and the CYP2C9 gene polymorphism are related. Methods: This study was conducted as a prospective case-control study. Fifty patients with RA and 50 healthy individuals were included in our study group. Blood from the controls and patients was drawn into ethylenediaminetetraacetic acid (EDTA)-containing tubes, and using a DNA isolation kit, DNA was isolated from leukocytes. Real-time polymerase chain reaction (RT-PCR) was used to assess the genotypes of CYPC9*2 and CYP2C9*3 with the LightCycler-CYP2C9 mutation detection kit. Results: The heterozygous CYP2C9*2 genotype was found to carry a 2.85-fold risk when compared with the controls (odds ratio [OR]=2.85, 95% confidence interval [CI]: 0.52–15.50; P=0.22); however, this risk was not statistically significant. It was found that people with the CYP2C9*3 heterozygous genotype had a statistically significant 2.79-fold higher risk compared to the controls (OR=2.79, 95% CI: 1.13–7.00 P=0.04). Conclusion: The heterozygous genotype of CYP2C9*3 may contribute to the onset of RA.