Background/Aims: Helicobacter pylori (H. pylori) can disseminate between couples. The present study compared the findings of gastric cancer screening between seronegative subjects according to the presence of an infected spouse. Materials and Methods: Follow-up data of seronegative subjects were analyzed among married couples who underwent gastric cancer screening via gastroscopy, serum pepsinogen, and anti-H. pylori IgG assays between January 2010 and May 2016. New detection rates of H. pylori

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... infection and gastric neoplasm at the follow-up screening were compared between seronegative subjects according to the H. pylori-infected status of spouse. Results: Among 246 seronegative subjects with an H. pylori-infected spouse, 92 underwent follow-up tests (case group). Among 278 seronegative subjects with seronegative spouse, 94 underwent follow-up tests (control group). The past infection rate was higher in the case group than in the control group (52/92 vs. 34/94; P=0.005). New H. pylori infection was diagnosed in three of the 92 cases and two of the 94 controls (3.2% vs. 2.1%; P=0.681). During the mean follow-up of 67.9±36.0 months, three adenocarcinomas and two adenomas (5/184) were newly detected among the cases and their spouses, whereas none (0/188) were detected among the controls and their spouses (2.7% vs. 0%; P=0.029). Conclusions: Gastric neoplasm occurred more frequently in couples with an H. pylori-infected spouse. Because the past infection rate is higher among seronegative subjects with an infected spouse, gastric cancer screening is recommended in both partners when the spouse is infected.