Cytokines gene polymorphisms have been implicated in susceptibility to ischemic stroke. This study aims to determine the influence of the polymorphism within the intron 2 of the interleukin- 1 receptor antagonist (IL-1Ra) gene on the susceptibility to stroke. A variable number of tandem repeats (VNTR) in intron 2 of the IL-1Ra gene was analyzed in 148 patients with stroke and 161 healthy volunteers from the same area. The carriage rate of allele 2 of IL-1Ra gene, low producer, was significantly higher in patients with stroke compared to the controls (29% vs 21% p = 0.02). Frequency of IL1RN1/IL1RN1 genotype in the patients was significantly lower than the controls (49% vs 66% p = 0.003). The distribution of homozygous genotypes of IL1RN2 was not different between the controls and stroke patients while the heterozygous genotype was more frequent among the patients. (39% vs 25%, respectively). Multiple logistic regression analysis demonstrated that individuals who carry allele 2 for IL-1Ra gene had a significantly higher risk for ischemic stroke with an odds ratio of 2.48 (95% CI, 1.67, 3.51, p = 0.006). These data suggest that allele 2 of the IL-1Ra intron 2 gene represents a susceptibility factor in the development of ischemic stroke.