This study aimed to determine whether the coding (A4889G) and noncoding region (T6235C) polymorphisms of the gene coding for cytochrome P4501A1 (CYP1A1), a xenobiotic-metabolizing enzyme responsible for the metabolism of carcinogenic polycyclic aromatic hydrocarbons, are involved in the pathogenesis of ischemic stroke in Turkish population. Study group consisted of 226 ischemic stroke patients and 113 controls. Genotypes were attained by allele-specific polymerase chain reaction (PCR) for A4889G and PCR/restriction fragment length polymorphism analysis for T6235C. Frequency of 6235C allele was significantly lower in patients (0.151) compared with controls (0.226, P = 0.015). Prevalence of hypertension and hypertension-associated ischemic stroke risk was lower for 6235C allele carriers. This allele decreased ischemic stroke risk twofold (adjusted odds ratio = 0.48, P = 0.005). There was almost no difference in 4889G allele frequencies in patients (0.445) and controls (0.425). However, prevalence of hypertension was lower in 4889G allele carriers when compared with the wild-type genotypes. In addition, risk of ischemic stroke for smoker and hypertensive individuals was lower when they have at least one 4889G allele. The present study demonstrated that CYP1A1 genetic variants contribute to interindividual variability in smoking- and hypertension-induced ischemic stroke risk.