We have previously reported that serum pepsinogen (PG) can quantify the level of gastric mucosal atrophy, and thatH. pylorieradication reduces cancer development in subjects with mild atrophy identified by serum PG levels. The aim of this study was to elucidate the predictive ability of serum PG levels for the development of metachronous gastric cancer (MGC) after endoscopic resection (ER) of primary cancer in association withH. pylorieradication. A retrospective chart review was performed, and 330 patients who underwent ER for initial early gastric cancer were enrolled. Presence or absence ofH. pylori, serum PG levels, and endoscopic atrophy at ER were evaluated.H. pylorieradication was performed at the patient's request after ER. The incidence of MGC in these patients was analyzed. Of 330 patients, 47 developed MGC. Endoscopic extensive atrophy was observed more frequently in patients with MGC (p= 0.001). Although PG I or PG II alone did not significantly differ according to development of MGC, the proportion of PG I/II ≤ 3.0, which is one of the criteria of PG test-positive, was significantly higher in patients with MGC (83vs. 69%,p= 0.04).H. pylorieradication after ER did not affect MGC development (p= 0.2). On multivariate analysis, serum PG I/II ratio ≤ 3.3 was significantly associated with the development of MGC (hazard ratio: 3.66, 95% confidence interval: 1.47–12.25,p= 0.004). The risk of MGC after ER could be quantitatively predicted by the PG I/II ratio regardless ofH. pyloristatus.