Abstract: Introduction: In view of the reported association of SNPs in the paraoxonase (PON1) gene with coronary artery disease (CAD), and the absence of conclusive data from India, we investigated the relationship of three SNPs at different loci (‐108C/T, L55M and Q192R) of the PON1 gene and their haplotypes with CAD among people residing in the northern plains of India. Materials and methods: One hundred and seventy-eight healthy controls and two hundred and four angiographically-proven CAD patients were genotyped using PCR-RFLP. Results: Of the three SNPs, only the R allele of Q192R polymorphism was associated with CAD (p<0.05). Two locus haplotypes QT (OR 0.55, p=0.0004, 95% CI 0.39–0.77, significant) and LQ (odds ratio 0.73, p=0.03, 95% CI 0.55–0.97, trend) showed protective effects, while haplotypes MR (OR=5.36, p=0.0001, 95% CI 2.045–14.049) and MC (OR=2.71, p=0.011, 95% CI 1.221–6.046) were associated with increased risk of CAD. MRT, a minor three-locus haplotype also displayed significant association (OR 4.93, 95% CI 1.7–13.5) with the disease. Significance was assessed after applying Bonferroni''s correction. Conclusions: Our study revealed that only one SNP at a single locus but several haplotype combinations of PON1 coding and promoter-region polymorphisms were associated with the risk of or protection against CAD. Thus, haplotype analysis brought better insights into the association of PON1 gene polymorphisms with CAD in Asian Indians. [Copyright &y& Elsevier]