<p><i>Helicobacter pylori (H. pylori)</i> screening reduces the incidence and mortality of gastric cancer (GC). This study evaluated the cost-effectiveness of incorporating <i>H. pylori</i> screening into the Korean National Gastric Cancer Screening Program. A Markov model was developed to evaluate the cost-effectiveness of adding <i>H. pylori</i> screening to the existing national endoscopic screening program. The model simulated a virtual cohort of individuals aged ≥ 40 years and compared the current biennial endoscopy-only strategy (S1) with eight intervention strategies involving one-time or repeated <i>H. pylori</i> eradication at varying ages and intervals. Sensitivity analyses were performed to test the robustness of the results. All intervention strategies resulted in higher QALYs and costs than S1. <i>H. pylori</i> screening at age 40 (S2) was the most cost-effective (ICUR = 3,892,429 KRW/QALY). Other cost-effective strategies included <i>H. pylori</i> screening at ages 40 and 50 years (S5), every 6 years from ages 40 to 60 years (S9), and every 4 years during the same period (S8). Health outcome comparisons showed reductions in both cumulative cancer incidence and mortality with eradication-based strategies. Adding <i>H. pylori</i> screening to Korea’s national endoscopic screening program is a cost-effective strategy for the prevention of gastric cancer. These findings support the potential integration of screening into existing national screening policies, with implications for improving health outcomes and optimizing healthcare resource use.</p>