The epistatic effects of ApoE (HhaI) and ApoA-I (PstI) genes as the genetic modulators of lipid levels were investigated in 165 angiographically verified CHD patients and 120 controls of Punjab, a northwest province of India. It has been revealed that of all the genotypic combinations of ApoE and ApoA-I, E4 allele carriers (E4+) with P1P2 genotype (ApoA-I/PstI) had higher risk of CHD (OR 2.99, CI 1.31-6.8, P<0.01) which exacerbated (OR 3.44, CI 1.45-8.15, P<0.01) after adjustment with the confounders. Individually, neither ApoA-I nor ApoE was found to be associated with TG levels however, pairwise epistasis (additive x additive model) explored their significant synergistic contributions with raised TG levels (P<0.01).