Objective. Reactive oxygen species an important role in the pathogenesis of cerebrovascular disorders. NAD(P)H oxidases are one of the main sources of superoxide anions in cerebral arteries. NAD(P)H oxidase represents molecular complex and its p22phox subunit is coded by the CYBA gene located in the long arm of chromosome 16. We studied the association between the 640A>G polymorphism (rs1049255) of the CYBA gene with the risk of stroke in the Russian population. Material and methods. Authors examined 887 people: 445 stroke patients, including 393 patients with ischemic stroke and 52 patients with hemorrhagic stroke, and 442 healthy people (controls). Genotyping was performed using real-time PCR and TaqMan allele discrimination assays. Results. It was found that carriers of the heterozygous genotype 640AG of the CYBA gene were at a lower risk of stroke compared to the controls (OR=0.77, 95% CI=0.59—1.01, p=0.05). The stratified analysis showed that the genotype 640AG was associated with decreased risk of ischemic stroke (OR=0.75, 95% CI=0.57—0.99, p=0.04). Conclusion. The present study is the first to show that polymorphism 640A>G of the CYBA gene is associated with the risk of ischemic stroke.