Subjects with a high-negative titer (3-9.9 U/ml) of serum anti- () antibody represent a heterogeneous group of currently -infected, -uninfected, and previously -infected cases. We investigated the characteristics of subjects with a high-negative titer during a medical check-up and the utility of infection score, the sum of scores of endoscopic findings based on the Kyoto Classification of Gastritis, for diagnosing infection. Subjects with C-urea breath test-positive or stool antigen test-positive were diagnosed as currently -infected. Although around half of subjects with a high-negative titer were after eradication therapy (48.6%), currently -infected were considerably confirmed (11.7%). infection score showed a high value of area under the receiver operating characteristic curve [0.92; 95% confidence interval (CI), 0.84-1.00] with the most suitable cut-off value of 1.0 (sensitivity: 0.92; specificity: 0.90). Multivariate logistic regression analysis revealed that infection score was an independent factor associated with increased prevalence of infection (odds ratio, 9.53; 95% CI, 2.64-34.40; <0.001). Currently -infected subjects were considerably included among the subjects with a high-negative titer, and the Kyoto Classification of Gastritis was useful to predict current infection.