Purpose. Single nucleotide polymorphisms of the CYBA gene may modify the risk of coronary artery disease (CAD). The aim of the present study was to investigate whether the (⁎)49A>G (rs7195830) polymorphism is associated with CAD. Materials and Methods. CYBA gene (⁎)49A>G polymorphism was determined in 481 subjects: 242 patients with premature CAD and 239 age and sex matched controls using the fluorescently labeled allele-specific oligonucleotides method. Results. The frequency of the (⁎)49G allele carrier state was significantly higher in patients than in controls (84.8% versus 76.6%, resp., P = 0.020), as well as the frequency of the (⁎)49G allele (62.2% versus 54.0%, P = 0.009). Both factors were associated with CAD in the analyzed population (OR = 1.70, 95% CI: 1.04-2.76 for GG+AG versus AA and OR = 1.40, 95% CI: 1.08-1.83 for (⁎)49G versus (⁎)49A). Carrier state of the (⁎)49G allele was a stronger and independent risk factor for CAD among women (OR = 4.35, 95% CI: 1.50-13.20, P = 0.002), as well as the (⁎)49G allele (OR = 2.25, 95% CI: 1.34-3.77, P = 0.001). The (⁎)49G allele carrier state was also associated with left ventricular hypertrophy in patients with coronary artery disease (P = 0.015). Conclusion. The CYBA gene (⁎)49A>G polymorphism modifies the risk of coronary artery disease.