Objectives: Oxidative stress is a known risk factor for the pathogenesis of atherosclerosis, the main cause of ischemic stroke. Glutathione S-transferase (GST) omega-1 and omega-2, members of phase II enzymes, play a role in the antioxidant system. The single nucleotide polymorphisms (SNPs), C419A and A424G in GST omega genes can cause a decrease in enzyme activity. The aim of this study was to investigate the possible association between these polymorphisms and ischemic stroke risk in a Turkish population. Methods: The genotypes and allele frequencies for 239 patients and 130 controls were determined by the PCR/RFLP method. No significant differences were found between patients and controls in terms of genotype and allele frequencies. Results: The frequency of the polymorphic ‘A’ allele was 0.358 in patients and 0.342 in controls for the C419A polymorphism in the GSTO1 gene. The frequency of the polymorphic ‘G’ allele for GSTO2 A424G SNP was 0.370 in patients and 0.404 in controls. The combined homozygous wild type genotype ‘CCAG’ was significantly higher in control group than in the patients. Conclusion: No significant difference was observed between the stroke patients and controls in terms of genotypes and allele distributions. Double combine haplotype CCAA was found to be protective against ischemic stroke when compare to other haplotypes. However, different genotypes of GSTO1 and GSTO2 were observed to have effects on stroke risk in subgroups of diabetics and smokers. In conclusion, the current study is the first to report this finding.