Cholesteryl ester transfer protein (CETP) is involved in a key pathway of reverse cholesterol transport implicated in atherosclerosis and coronary heart disease. CETP gene is known to have many single nucleotide polymorphisms which have been associated with CETP activity and plasma high density lipoprotein cholesterol (HDL-C) concentrations. No data on the prevalence of these polymorphisms and their phenotypic association is available in South Indian population.Three CETP polymorphisms: TaqIB, −629C/A and I405V were studied in 171 healthy volunteers from Tamilnadu, a major population of South India. Subjects were clinically examined and lipid profile was estimated. Genotyping was performed by PCR-RFLP and genotype frequencies estimated.The allele frequencies of TaqIB: B1 allele was 0.51; −629C/A: C allele was 0.36; and that of I405V: I allele was 0.47. Study of association between these three polymorphisms and plasma lipid concentrations revealed no significant differences in lipid parameters between genotypes. A gender based subgroup analysis revealed a significant increase in HDL-C in men with B2B2 genotype and decrease in TG in B1B2 genotype. Analysis of the combined effect of multiple mutant genotypes revealed that as the number of mutant genotypes increased, the concentrations of low density lipoprotein-cholesterol (LDL-C), HDL-C and total cholesterol (TC) increased whereas that of triglyceride (TG) decreased in the group of three mutant genotypes significantly.The frequency of B2 and A alleles of TaqIB and −629C/A polymorphisms were highest in Tamilian population when compared to other major ethnic groups while that of V allele of I405V polymorphism is between Caucasians and African Americans. Taq1B polymorphism was associated with HDL-C and TG concentrations only in men. Combination of these three polymorphisms was significantly associated with lipid profile than the individual polymorphisms.