Objective (s): Apolipoprotein E genotype (APOE) polymorphism affects lipid levels and CORONARY artery disease (CAD) risk. The aim of this study was to study the association of the Apolipoprotein E genotypes with CORONARY artery disease in the Iranian population.Materials and Methods: The Apolipoprotein E genotype in DNA samples extracted from 66 CAD+ patients and 61 control subjects by restricting enzyme digestion of amplified exon 4 APOE gene was determined.Results: The ε3 allele was found at similar frequency in control subjects (88.5%) and ATHEROSCLEROSIS patients (83.3%) (P=0.314). Our results showed that the frequency of the e3/e3 and e3/e4 genotypes increased in three-vessel-disease patients and the frequency of e2/e2 genotype increased in one-vessel-disease patients.Conclusion: e3/e3 and e3/e4 genotypes are suggested to be predisposing factors, which, in combination with environmental factors, may trigger the degree of luminal narrowing. The possible mechanisms remain elusive and require further studies.