Our previous epidemiologic study reported that NAD(P)H:quinone oxidoreductase 1 (NQO1) 609C/C with full enzyme activity was a high risk genotype for Helicobacter pylori (H. pylori) seropositivity. Since NQO1 stabilizes ornithine decarboxylase (ODC), which attenuates the innate immune response through elevated polyamines, ODC functional polymorphisms may also influence H. pylori seropositivity. This study aimed to examine the association with ODC A317G polymorphism, as well as the modification by NQO1 C609T. The two polymorphisms were determined by polymerase chain reaction with confronting two-pair primers (PCR-CTPP) among 465 health checkup examinees in Nagoya. The ODC A317G genotype frequency was 35.9% for A/A, 49.3% for A/G, and 14.8% for G/G. The sex-age-adjusted odds ratio (OR) of the ODC gene for H. pylori seropositivity was not significant (OR = 1.09 for G/A and OR = 1.02 for G/G, relative to A/A). Among subjects with any NQO1 genotype, no association was observed between the ODC ploymorphism and H. pylori seropositivity. Results of the present study did not support the hypothesis that the different genetic traits in the ODC-polyamine pathway are associated with susceptibility to persistent H. pylori infection. The higher frequency of the ODC 317A allele in the Japanese population than that in the Caucasian population is firstly reported. The genetic traits through the ODC-polyamine pathway will be further investigated.