Background: There are limited data evaluating the cost-effectiveness of gastric cancer screening using endoscopy or upper gastrointestinal x-ray in the general population. Objective: To evaluate the cost-effectiveness of population-based screening for gastric cancer in South Korea by decision analysis. Methods: A time-dependent Markov model for gastric cancer was constructed for healthy adults 30 years of age and older, and a deterministic sensitivity analysis was performed. Cost-utility analysis with multiple strategies was conducted to compare the costs and effects of 13 different screening alternatives with respect to the following eligibility criteria: age at the beginning of screening, screening interval, and screening method. The main outcome measurement was the incremental cost-effectiveness ratio. Results: The results revealed that annual endoscopic screening from ages 50-80 was the most cost-effective for the male population. In the females, biennial endoscopy screening from ages 50-80 was calculated as the most cost-effective strategy among the 12 screening alternatives. The most cost-effective screening strategy may be adjustable according to the screening costs and the distribution of cancer stage at screening. The limitation was that effectiveness data were obtained from published sources. Conclusions: Using the threshold of $19,162 per quality-adjusted life year on the basis of the Korean gross domestic product (2008), as suggested by the World Health Organization, endoscopic gastric cancer screening starting at the age of 50 years was highly cost-effective in the Korean population. The national recommendation for gastric cancer screening should consider the starting age of screening, the screening interval, and the screening modality.