Background: Platelet endothelial cell adhesion molecule-1 (PECAM-1) plays a key rolein the transendothelial migration of circulating leukocytes, a characteristic event invascular inflammation leading to atherosclerotic plaque formation.Objective: The aim of the present study was to determine the role of PECAM-1 in thedevelopment of coronary artery disease (CAD).Patients and Methods: Two single nucleotide polymorphisms (SNPs) of PECAM-1gene: C+373G (Leu125Val) at exon 3 and G+1688A (Ser563Asn) at exon 8 wereanalyzed in 50 angiographically documented (> 70% stenosis) Egyptian patients withCAD and 40 age- and sex-matched controls using a polymerase chain reaction-restrictionfragment length polymorphism (PCR-RFLP) strategy.Results: Results demonstrated that genotype and allele frequencies for the Leu125Val(C+373G) polymorphism of PECAM-1 gene showed increase in CAD patients comparedto controls (p=0.007), whereas, regarding the allele frequencies and genotype distributionsof Ser563Asn (G+1688A) polymorphism, a similar trend was observed, though thedifference did not reach significance (p=0.302). It was also found that the homozygousgenotype combination of GG (for Leu125Val) and AA (for Ser563Asn) was significantlyincreased in patients compared to controls (24% and 7.5% respectively, p<0.05). Therewas a significant association between Ser563Asn polymorphism and the number ofoccluded coronary vessels.Conclusion: This demonstrates a possible involvement of Leu125Val polymorphism ofPECAM-1 gene in the development of CAD in Egyptian patients. Therefore, a betterunderstanding of the role of PECAM-1 molecule in this complex mechanism is of pivotalsignificance in further development of innovative and suitable medical therapies in thefuture.