Population endoscopic screening for gastric cancer is generally deemed not to be cost-effective except in Japan, where its prevalence is very high. However, in the absence of screening, patients present with advanced disease, and prognosis is poor. We conducted a cost utility analysis to determine whether endoscopic screening for stomach cancer in intermediate-risk population would be cost-effective and to better define the high-risk groups in the population who would benefit from such strategy. Cost-effectiveness analysis was performed by using a Markov Model. Simulation was performed on Singapore (intermediate-risk) population and various high-risk subgroups. Comparison was made between 2-yearly endoscopic mass screening program versus no screening. Data sources were extracted from relevant studies published from 1980-2004 identified via systematic PUBMED search. Main outcome measures were deaths caused by stomach cancer averted, cost per life saved, and incremental cost-effectiveness ratio expressed as cost per quality-adjusted life year (QALY) saved. Screening of high-risk group of Chinese men (age-standardized rate, 25.9/100,000) from 50-70 years old is highly cost-effective, with cost benefit of United States $26,836 per QALY. Screening this cohort of 199,000 subjects prevents 743 stomach cancer deaths and saves 8234 absolute life years. Cost of averting 1 cancer death is United States $247,600. Cost-effectiveness was most sensitive to incidence of stomach cancer and cost of screening endoscopy. Screening of stomach cancer in moderate to high-risk population subgroups is cost-effective. Targeted screening strategies for stomach cancer should be explored.