Recent studies have suggested that Helicobacter pylori (H. pylori) infection might be a risk factor for atherosclerosis. Since the bacterium has not been isolated from atherosclerotic lesions, a direct role in atherogenesis is not plausible. We examined associations of plasma total homocysteine (tHcy) and serum folate, independent risk factors for atherosclerosis, with H. pylori infection and subsequent gastric atrophy among 174 patients (78 males and 96 females) aged 20 to 73 years, who visited an H. pylori eradication clinic of Nagoya University from July 2004 to October 2005. Polymorphism genotyping was conducted for methylenetetrahydrofolate reductase (MTHFR) C677T and thymidylate synthase (TS) 28-bp tandem repeats by PCR with confronting two-pair primers and PCR, respectively. H. pylori infection and gastric atrophy were not significantly associated with hyperhomocysteinemia (tHcy > or = 12 nmol/ml), when adjusted by sex, age, smoking, alcohol, and genotypes of MTHFR and TS. The adjusted odds ratio of gastric atrophy for low folate level (< or = 4 mg/ml) was 0.21 (95% confidence interval = 0.05-0.78). The associations of tHcy with serum folate and MTHFR genotype were clearly observed in this dataset. The present study demonstrated that folate and MTHFR genotype were the deterministic factors of plasma tHcy, but not H. pylori infection and subsequent gastric atrophy, indicating that even if H. pylori infection influences the risk of atherosclerosis, the influence may not be through the elevation of homocysteine.