Background: Coronary artery disease (CAD) is one of the cardiovascular diseases, which is caused by a reduced amount of oxygen and blood that goes to the heart. CAD includes stable angina, unstable angina, myocardial infarction, and sudden cardiac death. It is a common cause of death in both men and women. The environmental and genetic factors are involved in the development of CAD. Multiple gene polymorphisms are risk factors of CAD. Objective: To evaluate the association between EL 584C/T polymorphism, CAD risk, and lipid profile in an Egyptian population. Methods: This is a case‐control study. The patients were classified into three groups: Group A: Control group, this group included 42 apparently healthy people. Group B: included 42 subjects diagnosed with previous myocardial infarction (MI). Group C: included 42 subjects diagnosed with unstable angina (UA). Results: The frequencies of TT and CT genotypes and T allele were higher in control healthy individuals than CAD patients. In addition, the risk of CAD was significantly lower in individuals carrying T allele (P = 0.001). Serum highdensity lipoprotein (HDL) levels were significantly higher in healthy individuals and CAD patients (MI and UA patients) carrying EL 584 T allele compared with those carrying CC genotype (P ≤ 0.001). By multiple logistic regression, we found that the protective effect of T allele remained significant (P = 0.005) and it decreased the risk of CAD independent of plasma HDL levels. Conclusion: There was a significant difference between 584C/T polymorphism in the EL gene and CAD and HDL level. T‐allele carriers had a higher HDL level and were protected from CAD. T allele was significantly associated with the decreased risk of CAD independent of plasma HDL levels. KEYWORDS coronary artery disease, endothelial lipase, high‐density lipoprotein