Objective To compare the effectiveness and safety of endoscopic submucosal dissection (ESD) with endoscopic piecemeal mucosal resection (EPMR) for early esophageal cancer and precancerous lesions with length more than 5 cm. Methods A retrospective analysis was performed on the data of 85 patients diagnosed as early esophageal cancer and precancerous lesions with length more than 5 cm in Fujian Medical Association of Early Esophageal Carcinoma from January 2012 to July 2017. The patients were divided into ESD group (52 cases) and EPMR group (33 cases), and the effectiveness and safety between two groups were compared. Results There was no significant difference on the complete resection rate between the two groups [86.5% (45/52) VS 87.9% (29/33), P>0.05]. The operative time (58.53±30.50 min VS 32.06±9.12 min), postoperative fasting time (4.18±1.30 d VS 3.67±0.96 d), postoperative hospital-stay time (7.45±2.44 d VS 6.54±1.73 d), and postoperative antibiotics using time (3.48±2.33 d VS 1.96±2.20 d) in ESD group were higher than those in EPMR group (all P<0.05). There were no significant difference in the rate of intraoperative complication and short-term postoperative complication, such as fever, chest pain, and postoperative bleeding, between the two groups (all P>0.05). But the postoperative stricture rate of ESD group was higher than that of EPMR group [23.1% (12/52) VS 6.1% (2/33), P<0.05]. During the follow-up of 3-63 months, 5 cases recurred in ESD group and 1 case in EPMR group, with no significant difference (P>0.05). Conclusion ESD and EPMR have equivalent efficacy and safety on the treatment of early esophageal cancer and precancerous lesion. EPMR has a shorter operative time, lower rate of post-operative stricture, and is easier to master.