Background and Aims: The aim of this study was to assess the association between the L-selectin Phe206Leu polymorphism and coronary artery disease. Methods: A total of 322 patients (221 men and 101 women) with coronary artery disease in one or more vessels documented by angiography were studied; 157 subjects (85 men and 72 women) without atherosclerosis were included as controls. All subjects were genotyped for the L-selectin Phe206Leu gene polymorphism using polymerase chain reaction with sequence-specific primer (PCR-SSP). To assess disease severity, all patients were classified by numbers of coronary arteries with 50% stenosis. Results: A significantly increased frequency of the 206Leu mutant allele was observed in patients with coronary artery disease compared to the controls. The 206Leu allele frequency occurred in 42% of the patients with coronary artery disease compared to 30% of the controls (p < 0.009). No association was found between the severity of coronary artery disease and the L-selectin Phe206Leu polymorphism. Conclusion: Our findings suggest that carriage of L-selectin 206Leu mutant allele could contribute to susceptibility of Iranian individuals to contracting coronary artery disease.