Background The oxidative modification of low-density lipoprotein in the artery wall is currently believed to be central to the pathogenesis of atherosclerosis. Paraoxonase (PON1), an enzyme located on high-density lipoprotein (HDL), can prevent low-density lipoprotein (LDL) from oxidation at a certain extent. Recent studies show two other members of paraoxonase gene family, PON2 and PON3, possess antioxidant properties similar to PON1. The aim of the present study was to explore the role of PON gene cluster on coronary heart disease (CHD) in Chinese Han women.Methods Seven polymorphisms including PON1 -107C>T, -162G>A, -831G>A, R160G, Q192R, PON2 S311C, and PON3 -133C>A were genotyped in 184 female patients with CHD and 239 female controls. The plasma PON1 activity toward phenylacetate was determined in 50 cases and 50 controls randomly selected. Results The plasma PON1 activities were significantly lower in cases than in controls. Individual SNP analysis showed that cases had significantly higher frequencies of PON1 -107T, -831G and PON2 311S alleles than controls. The genotype distributions of -107C>T were also significantly different between two groups. The odds ratios for the development of CHD were 1.66 for -107TC carriers and 2.0 for -107TT carriers, compared with -107CC carriers. Haplotype analyses showed that the distributions of haplotypes comprised of PON1 -107C>T and PON2 S311C were significantly different between cases and controls, with cases having higher frequency of T-S haplotype (44.8% vs. 36.3%, P=0.013). The T-S haplotype remained significantly associated with CHD after adjusting environmental risk factors (P=0.0069).Conclusions This association study suggested that lower plasma PON1 activity increased the risk of CHD in Chinese woman, which may be mediated by the higher frequency of -107T allele in cases. Haplotype analyses indicated that there might be some synergistic effects between the PON1 -107C>T and PON2 S311C polymorphisms.