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Abstract Aim This study aimed to explore the efficacy and safety of endoscopic submucosal dissection/endoscopic mucosal resection (ESD/EMR), laparoscopic-assisted radical gastrectomy (LARG), and open radical gastrectomy (ORG) in early-stage gastric cancer. Methods A total of 417 patients with early-stage gastric cancer who were admitted in two hospitals from January 1, 2014 to July 31, 2017 were selected; the patients were divided into the ESD/EMR group (139 cases), LARG group (108 cases), and ORG group (170 cases) according to the operation methods used. The baseline data, economic cost of health, oncologic characteristics, postoperative complications, 5-year overall survival and disease-free survival, and risk factors of death were compared and analyzed. Results No significant difference was observed in the baseline data among the three patient groups (P > 0.05). The total hospitalization days, operation time, postoperative fluid intake time, hospitalization expenses, and proportion of antibiotic use rate in the ESD/EMR group were lesser than those in other groups (P 0.05). The 5-year postoperative survival rates of patients in the three groups were 94.2% (ESD/EMR), 93.5% (LARG), and 94.7% (ORG), respectively, with no significant differences (P > 0.05). The binary logistics multivariate analysis showed that the tumor size, invasion depth, vascular invasion, and differentiated degree were risk factors for death in patients with gastric cancer. Conclusions No significant difference was observed between ESD/EMR and radical surgery. However, standardized criteria for excluding metastatic lymph nodes should be established to promote ESD/EMR.