Background A combination of assays for the presence of serum anti-Helicobacter pylori IgG antibody (HPA) and serum pepsinogen (PG) concentrations can be used to screen for gastric cancer risk. In Japan, this "ABC method" is considered an effective means of stratifying gastric cancer risk. This study aimed to ascertain its costeffectiveness for assessing gastric cancer risk. Methods A Markov model was constructed to compare the cost-effectiveness of two strategies for gastric cancer-risk screening over a 30-year period: the ABC method, which uses a combination of assessing the presence of and measuring serum PG concentrations and scheduling endoscopies accordingly, and annual endoscopic screening. Clinical and epidemiological data on variables in the model were obtained from published reports. Analyses were made from the perspective of the Japanese health care payer. Results According to base-case analysis, the ABC method cost less than annual endoscopie screening (64,489 vs. 64,074 USD) and saved more lives (18.16 vs. 18.30 quality-adjusted life years). One-way analyses confirmed the robustness of the cost-effectiveness results. The probability that the ABC method is cost-effective in Japanese individuals aged 50 years was 0.997. Conclusions A combination of HPA and serum PG assays, plus scheduling endoscopy accordingly, is a cost-effective method of screening for gastric cancer risk in Japan.