Apolipoprotein E is a fundamental component of various lipoproteins and plays substantial role in cholesterol/lipid transport among cells of various tissues. The ApoE gene is polymorphic with three alleles ε2, ε3, and ε4, coding for isoforms E2, E3, and E4 having different binding inclination for corresponding receptors. This work aimed to investigate the association between ApoE gene polymorphism and coronary artery disease (CAD) in Kashmiri population. APOE genotyping was done by polymerase chain reaction-restriction fragment length polymorphism. Our study indicated ApoE ε3/ε3 to be the most common genotype in both CAD and control group. The frequency of ε2, ε3, and ε4 alleles of ApoE gene in cases was observed to be 0.06, 0.72, and 0.20, while in control subjects it was 0.075, 0.82, and 0.11, respectively. A significant difference was found between cases and controls with respect to TC, LDL, and HDL levels. Our data showed that frequency of ε4/ε4, ε4/ε3 genotype and ε4 allele was significantly higher in cases than in controls (p = 0.02, p = 0.004, p < 0.001 respectively). Moreover, the CAD patients carrying ε4 allele had significantly higher TC and LDL levels (p value <0.01). Thus our data showed a significant association of ApoE ε4 allele with the risk of CAD. The data revealed that ApoE ε4 allele is associated with increased risk of CAD and increased levels LDL and TC in Kashmiri population.