Our previous study revealed that a polymorphism of the interleukin (IL) 1B gene, encoding the pro-inflammatory cytokine IL-1 beta, influenced the prevalence of persistent Helicobacter pylori (HP) infection. In this paper, a polymorphism of another inflammation-related enzyme, myeloperoxidase (MPO), was examined with respect to association with the HP infection. The polymorphism is due to a G-to-A transition at - 463 in the promoter region of MPO. The G allele is the wild type with normal expression, while the A allele is a low expression allele. The subjects were 241 non-cancer outpatients (118 males and 123 females) aged 39 to 69 who participated in an HP eradication program at Aichi Cancer Center Hospital. High-molecular weight Campylobacter-Associated-Protein (HM-CAP) ELISA (Enteric Products Ins., Westbury, NY) was used for the identification of HP-infected participants. The frequency was 79.7% (192 / 241) for the GG genotype, 19.5% (47 / 241) for the GA genotype, and 0.8% (2 / 241) for the AA genotype. The sex-age-adjusted odds ratio (OR) relative to GG was 0.69 (95% confidence interval (CI), 0.35 -- 1.35) for individuals with the A allele, but among male participants the OR was 0.31 (0.11 -- 0.84). Subgroup analysis revealed significantly reduced ORs with the GA / AA genotypes for current smokers (0.19, 0.04 -- 0.96), and for those who were occasional / no milk drinkers (0.25, 0.09 -- 0.72). These findings are consistent with the results for IL-1B in our earlier study, suggesting that inflammatory responses in the gastric mucosa may influence persistent HP infection, and that smoking and milk intake may be effect-modifiers.