Background: Helicobacter pylori (HP) eradication is recommended after endoscopic treatment of early gastric cancer (EGC). However, although cases of spontaneous resolution of HP after gastrectomy due to changes in the environment have been reported, there is no evidence for the efficacy of HP eradication in suppressing atypical carcinogenesis after gastrectomy. Herein, we prospectively studied the spontaneous disappearance rate of HP after gastrectomy in patients with gastric cancer.Methods: From April 2016 to May 2020, 100 patients who underwent gastrectomy with preoperatively confirmed HP in the stool antigen test were tested one year after surgery in this trial. There were 20 cases of total gastrectomy (TG), 9 cases of proximal gastrectomy (PG), and 71 cases of distal gastrectomy (DG) consisting of 29 cases with Billroth-1 (B-1) reconstruction and 42 cases with Roux-en-Y (RY) reconstruction.Results: After one year, 46 patients were positive, and 54 patients were negative for HP infection. In the univariate analysis, surgical procedure, pathological stage, and the presence of postoperative chemotherapy were significant factors for spontaneous resolution of HP infection. In multivariate analysis, only the surgical technique of TG remained as an independent factor. There were no significant differences in the rates of HP resolution between B-1 and RY reconstruction.Conclusions: One year after gastrectomy, spontaneous disappearance of HP was observed in approximately half of the patients. Therefore, HP eradication in patients with gastric cancer in the early postoperative period is not necessary, even if they are preoperatively positive for HP infection.Trial registration: Registration number: University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN ID: UMIN000046614); Registration date: 12/01/2022, retrospectively registered.