Background: Population-based Helicobacter pylori (H. pylori) eradication reduces gastric cancer (GC) risk. 
Objectives: We conducted an economic evaluation of H. pylori screen-and-treat strategy for GC prevention alongside a large-scale, cluster-randomized, controlled trial.
Methods: A within-trial economic evaluation was performed from the healthcare system perspective based on the Mass Intervention Trial in Linqu, Shandong Province, China (n=180,284, 2011-2022). H. pylori-positive individuals received anti-H. pylori treatment or symptom alleviation treatment. We examined the incremental mean cost per participant and incremental effect on GC prevention for the cost-effectiveness analysis, and the incremental quality-adjusted life-years (QALYs) and incremental net monetary benefit (INMB) for the cost-utility analysis.
Results: During 11.8 years’ follow-up, the mean cost per participant was reduced by $11.03 (95% confidence interval (CI): -$4.29, $24.27) for anti-H. pylori treatment, and by $16.35 (95% CI: $3.42, $27.68) for successful eradication, compared with that for symptom alleviation treatment. Anti-H. pylori treatment yielded an estimated reduction of 53.37 (95% CI: 0.18, 99.47) GC cases, and averted 0.0016 QALY loss (95% CI: 0.0008, 0.0025) per participant (INMB=$19.80, 95%CI: $4.77, $34.83). Successful eradication was particularly cost-saving with an estimated reduction of 73.94 (95%CI: 14.07, 124.49) GC cases, and an average gain of 0.0019 QALY (95%CI: 0.0008, 0.0030) per participant (INMB=$26.77, 95%CI: $13.28, $40.25). Furthermore, H. pylori treatment demonstrated significant cost savings for individuals <45 years. Economic benefits remained even when considering trial participants in the real-world screen-and-treat scenario and providing full insurance coverage for H. pylori treatment for individuals aged<45 years. 
Conclusions/Implications for practice or policy: Community-based H. pylori screening and treatment was cost-effective for GC prevention and improvement of QALY based on a large-scale intervention trial, supporting the implementation of mass H. pylori screening and treatment as a public health initiative in China and globally. In countries with a high GC burden, policymakers should consider expanding medical insurance coverage to include H. pylori eradication when adopting H. pylori screen-and-treat policy, with due consideration of local epidemiological and healthcare context. .Chictr.org.cn no. ChiCTR-TRC-10000979.

Dr. ?Wen-Qing Li is the Deputy Director and Professor of the Center for Clinical Epidemiology, Peking University Cancer Hospital, and a principal investigator of the State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers in China. Dr. Li's area of expertise is in cancer epidemiology and cancer prevention, focusing on risk assessment, precise prevention, and control of gastric cancer as the main line of his research, and has authored over 200 publications. He is an awardee of the National Youth Award of China, Young Cancer Scientist Award of China, and Distinguished Youth Talent Award of Beijing. Dr. Li serves as a delegate to the National Congress of Chinese Society of Science and Technology and is a council member of the Chinese Anti-Cancer Association (CACA). He is the Deputy Chair of the Cancer Epidemiology Professional Committee of CACA and the Youth Council of the Beijing Anti-Cancer Association.