Objective To investigate the clinical safety and efficacy of endoscopic submucosal dissection (ESD) in the treatment of superficial lesions of gastric mucosa, and to analyze the related factors and management of complications of ESD treatment. Methods We retrospectively analyzed the clinical data of 116 patients with superficial lesions of gastric mucosa undergoing ESD, evaluated the efficacy of ESD, observed the appearance and treatment of complications of ESD, and analyzed the factors influencing intraoperative and postoperative complications. Results The ESD was successfully completed in all cases, with the en bloc resection rate being 99.1% (115/116) and the complete cure rate being 95.7% (111/116). The average tumor size was (25.0±11.6) mm, and the average operation time was (56.6±20.5) min. The incidence rates of acute slight bleeding during operation and delayed bleeding were 3.4% (4/116) and 0.9% (1/116), respectively, without acute hemorrhage; 5 cases of bleeding were successfully treated by coagulation hemostasis and hemoclip. Perforation occured in 3 cases (2.6%) and was closed by hemoclip during operation; all cases of perforation had no pneumoperitoneum and were treated successfully by conservative method. Review at 2 months after ESD showed that the ulcer healing rate was 100%. The average follow-up time was (20.3±5.1) months. Gastric angle (χ²=7.937, P=0.01) and the postoperative pathological results as early carcinoma (χ²=9.145, P=0.005) were risk factors influencing the intraoperative bleeding and perforation complications. Conclusion ESD is a safe and effective minimally invasive treatment, and has high operation success rate. The prevention of bleeding should be emphasized during and after ESD operation. Perforation complications also should be discovered during the early stage of operation, which can contribute to complete effective closure of perforation under endoscope in most cases.