infection and a family history of gastric cancer are the main risk factors for gastric cancer. Whether treatment to eradicate can reduce the risk of gastric cancer in persons with a family history of gastric cancer in first-degree relatives is unknown. In this single-center, double-blind, placebo-controlled trial, we screened 3100 first-degree relatives of patients with gastric cancer. We randomly assigned 1838 participants with infection to receive either eradication therapy (lansoprazole 30 mg, amoxicillin 1000 mg, and clarithromycin 500 mg, each taken twice daily for 7 days) or placebo. The primary outcome was development of gastric cancer. A prespecified secondary outcome was development of gastric cancer according to eradication status, assessed during the follow-up period. A total of 1676 participants were included in the modified intention-to-treat population for the analysis of the primary outcome (832 in the treatment group and 844 in the placebo group). During a median follow-up of 9.2 years, gastric cancer developed in 10 participants (1.2%) in the treatment group and in 23 (2.7%) in the placebo group (hazard ratio, 0.45; 95% confidence interval CI, 0.21 to 0.94; P = 0.03 by log-rank test). Among the 10 participants in the treatment group in whom gastric cancer developed, 5 (50.0%) had persistent infection. Gastric cancer developed in 0.8% of participants (5 of 608) in whom infection was eradicated and in 2.9% of participants (28 of 979) who had persistent infection (hazard ratio, 0.27; 95% CI, 0.10 to 0.70). Adverse events were mild and were more common in the treatment group than in the placebo group (53.0% vs. 19.1%; P<0.001). Among persons with infection who had a family history of gastric cancer in first-degree relatives, eradication treatment reduced the risk of gastric cancer. (Funded by the National Cancer Center, South Korea; ClinicalTrials.gov number, NCT01678027.).