The association between Helicobacter pylori (H. pylori) infection and coronary artery disease, as well as the association between H. pylori infection and classic coronary risk factors, is controversial in patients from Western countries. The high prevalence of H. pylori infection in Japanese subjects enables an examination of these associations in a large population, especially in young patients, because coronary risk factors may be more strongly associated with younger individuals than with older individuals. The IgG seropositivity to H. pylori was assessed in 618 cases with acute myocardial infarction (AMI) and in 967 controls. The prevalence of seropositivity to H. pylori was similar between cases and controls, but in subjects younger than 55 years, the rate was significantly higher in cases than in controls (58.7% vs 43.3%, p = 0.009). After adjustment for age, gender, diabetes mellitus, hypertension, smoking, body mass index, total cholesterol, and high density lipoprotein cholesterol, the odds ratio for acute myocardial infarction was 2.97 (95% confidence interval, 1.37-6.41; p = 0.006). Worsening of classic coronary risk factors was not associated with H. pylori infection in subjects younger than 55 years. These results suggest that in younger individuals in Japan, H. pylori infection is significantly associated with AMI independent of the classic coronary risk factors.