To assess the benefits of intervention programs against Helicobacter pylori infection, we estimated the baseline curves of its incidence and prevalence. We developed a mathematical (compartmental) model of the intrinsic dynamics of H. pylori, which represents the natural history of infection and disease progression. Our model divided the population according to age, infection status, and clinical state. Case-patients were followed from birth to death. A proportion of the population acquired H. pylori infection and became ill with gastritis, duodenal ulcer, chronic atrophic gastritis, or gastric cancer. We simulated the change in transmissibility consistent with the incidence of gastric cancer and duodenal ulcer over time, as well as current H. pylori prevalence. In the United States, transmissibility of H. pylori has decreased to values so low that, should this trend continue, the organism will disappear from the population without targeted intervention; this process, however, will take more than a century.