Objectives: Stroke is currently the third leading cause of death and the biggest single cause of major disability worldwide. The purpose of this study was to determine the association between intercellular adhesion molecule-1(ICAM-1) gene K469E polymorphism and ischemic stroke and to detect whether the ICAM-1 469E allele is important in the pathogenesis of ischemic stroke.Subjects & Methods: A case-control study was conducted. Genotypes of ICAM-1 K469E gene were detected by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) in 40 Egyptian patients with ischemic stroke and 40 healthy subjects as a control group. Serum ICAM-1 levels were measured by enzyme linked immunosorbent assay.Results: It was found that EK & EE genotypes frequencies were significantly higher in cases (75.5% and 5% respectively) than control group (37.5% and 0% respectively) P=0.000. It was found that E allele frequency was significantly higher in cases (43.8%) than control group (18.8%); P=0.001.The median ICAM-1 serum levels were significantly higher in cases 393.2 ng/l (371.4-1180.7) as compared to control group 346.3ng/l (310.8-431.7); P=0.001. Conclusion: In conclusion, these results suggest that ICAM-1 K469E gene polymorphism may influence the susceptibility to acquire ischemic stroke in a sample of Egyptian population.