Objective To assess the safety and efficacy of endoscopic submucosal dissection (ESD) in the treatment of early gastric cancer and precancerous lesion, so as to provide basis for its clinical application. Methods Clinical data of 214 patients with gastric mucosal lesion, who underwent ESD treatment in Digestive Endoscopy Center of Changhai Hospital of Second Military Medical University from Oct. 2012 to Aug. 2014, were retrospectively analyzed to assess the features such as the preoperative evaluation, pathology, ESD treatment and post-operative follow-up. Results Among 214 patients, 67 (31.3%) received narrow band imaging (NBI) examination, 39 (18.2%) NBI combined with magnifying endoscopy (ME), 50(23.4%) endoscopic ultrasonography (EUS), 50(23.4%) CT, and 192 (89.7%) biopsy during the pre-operative evaluation. Pathological results showed that, among all included patients, low-grade intraepithelial neoplasia accounted for 39.3%(84 cases), high-grade intraepithelial neoplasia 25.7%(55), well differentiated carcinoma 21.0%(45), moderately differentiated carcinoma 8.9%(19), and poorly differentiated carcinoma 5.1%(11). The en bloc resection rate of ESD was 96.3% and the complete resection rate was 92.1%. The operation time of ESD ranged from 14 min to 290 min, a mean of (59.9±49.6) min. There were two cases (0.9%) had severe intra-operative hemorrhage, two (0.9%) intraoperative perforation, five (2.3%) delayed hemorrhage, 0 delayed perforation and five (2.3%) recurrence. Conclusion ESD is a safe and effective method in the treatment of early gastric mucosal lesion. Comprehensive pre-operation evaluation is needed to avoid unnecessary or excessive ESD treatment. Regular follow-up after operation is effective to monitor residual tumor and recurrence.