Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. Endoscopic submucosal dissection (ESD) and gastrectomy with lymph node dissection are considered acceptable treatment modalities for early gastric cancer (EGC). In the last decade, ESD has become more favorable than surgery as it offers faster recovery, lower costs, and a superior quality of life when compared to gastrectomy. The aim of this study is to compare the long-term outcome of ESD versus surgery in EGC. We performed a systematic and comprehensive search of major reference databases (Medline, Embase, CINHAL) for all studies that compared the outcome of EGC for patients underwent ESD or surgery in the same cohort. A systematic review was conducted through November 2017, using pooled analysis to calculate 5-year overall survival (OS) rate, disease-specific survival (DSS) rate, disease-free survival (DFS) rate, and recurrence-free survival (RFS) rate of ESD versus gastrectomy. Five-year OS and DSS were similar between ESD and gastrectomy groups 96 versus 96% and 99.4 versus 99.2%, respectively. Likewise, DFS was similar in both groups 95.9 versus 98.5% odds ratio 1.86 (0.57-6.0) P=0.3. However, ESD had a lower RFS compared to surgery 92.4 versus 98.3% odds ratio 0.17 (0.1-4.9) P=0.001. Overall, there was a higher recurrence rate in patients who underwent ESD compared to surgery [40/2943 (1.4%) vs. 12/3116 (0.4) risk ratio (RR) 2.5 (1.3-4.8) P=0.005]. Moreover, synchronous and metachronous cancers were more prevalent in the ESD group compared to the surgery group [1.5 vs. 0.1% RR 5.7 (1.5-21.9) P=0.01] [16/1082 (1.5%) vs. 1/1485 (0.1%) RR 10.1 (5.9-17.1) P=0.0001]. Five-year OS, DSS and DFS were similar between ESD and surgery groups. However, recurrent, synchronous and metachronous cancers were more prevalent in patients treated by ESD compared to patients treated by surgery, resulting in a lower RFS. Adequate surveillance with upper endoscopy is crucial after ESD to detect early recurrence and metachronous lesions.