OBJECTIVES: Helicobacter pylori infection and the degree of chronic atrophic gastritis are significant predictors for the development of gastric cancer, especially in the Japanese population. A combination of assays for serum anti-Helicobacter pylori immunoglobulin G antibody (HPA) and serum pepsinogen (PG) levels can be used to identify gastric cancer risk. In Japan, this ABC method may be an effective approach for identifying high-risk individuals who should undergo gastric cancer screening. The present study’s purpose was to estimate the long-term cost-effectiveness of the ABC method for assessing the gastric cancer risk in a Japanese population. METHODS: We constructed a Markov cohort model to compare the lifetime expected cost of and life-years saved by two strategies: 1) the ABC method, using a combination of HPA and serum PG levels for cancer-risk screening, and 2) scheduled endoscopy, the strategy of conducting endoscopic surveillance yearly for everyone. The target population was 40 to 60-year-old Japanese individuals, who had not received H. pylori eradication therapy. Clinical and epidemiological data, including the model, were obtained from published literature. Analyses were conducted from the Japanese health care payer perspective. RESULTS: According to cohort simulation, the ABC method cost less than annual endoscopic screening (128,970 vs. 276,561 Japanese yen) and saved more lives (25.55 vs. 25.50 life years) in Japanese individuals aged 40 years. The results of individuals aged 50 and 60 years indicated prolonged life-years and a reduced cost. CONCLUSIONS: A combination of HPA and serum PG assays plus scheduling endoscopy accordingly is a cost-effective strategy of screening for gastric cancer risk in Japan. The present study’s result provides new evidence of the economic impact of H. pylori eradication and scheduled endoscopy on gastric cancer screening.