Introduction: The aim of this study was to investigate the interaction between CETP (Cholesteryl Ester Transfer Protein) polymorphisms and macronutrient intakes in relation to metabolic syndrome (MetS) and its components. Materials and Methods: In this matched nested case-control study, 441 MetS subjects and 844 controls were selected from among participants of the Tehran Lipid and Glucose Study. Dietary intake was determined using a valid and reliable food frequency questionnaire. Portions of DNA samples were genotyped with HumanOmniExpress-24-v1-0 bead chips (containing 649,932 SNP loci) in the Tehran cardio-metabolic genetic study. Results: Mean ages of men and women did not differ between cases and controls. Frequencies of the C (rs3764261) and A(rs5882) alleles were 62.9% and 62.1%, respectively, and did not differ in cases and controls. Compared to CC (rs3764261) genotype, low HDL-C risk was decreased in subjects with the AC+AA genotypes (P<0.001). Interactions were observed between Mono-unsaturated fatty acids, total fat intakes and rs5882 in relation to risk of low HDL-C (Pi=0.02 and 0.05, respectively). The risk of high blood pressure across quartiles of trans-fatty acid and cholesterol intake differed in rs5882 genotypes (Pi<0.05). Conclusions: Our findings demonstrated no interaction between rs3764261, rs5882 polymorphisms and macronutrient intakes in relation toMetS; neither were MUFA and trans-fatty acid intakes associated with rs5882 genotypes in relation to risk of high blood pressure and low HDL-C.