Endoscopic submucosal dissection (ESD) has been developed to overcome the limitations of endoscopic mucosal resection (EMR). We aimed to compare the outcomes of these two methods. Databases, including Pubmed, EMBASE, and The Cochrane Library, were searched to identify studies comparing ESD with EMR for premalignant and malignant lesions of the gastrointestinal tract. In a meta-analysis, primary end points were the en bloc resection rate and the curative resection rate; secondary end points were operation time, and rates of bleeding, perforation, and local recurrence. 15 nonrandomized studies (seven full-text and eight abstracts) were identified. Meta-analysis showed higher en bloc and curative resection rates (odds ratio [OR] 13.87, 95 %CI 10.12 - 18.99; OR 3.53, 95 %CI 2.57 - 4.84) irrespective of lesion size. Subgroup analysis showed higher en bloc and curative resection rates with ESD for esophageal, gastric, and colorectal neoplasms, and for lesions of size < 10 mm, 10 mm < 20 mm, and > 20 mm. Local recurrence was lower with ESD (OR 0.09, 95 %CI 0.04 - 0.18). But ESD was more time-consuming than EMR (weighted mean difference [WMD] 1.76; 95 %CI 0.60 - 2.92), and showed high procedure-related bleeding and perforation rates (OR 2.20, 95 %CI 1.58 - 3.07; OR 4.09, 95 %CI 2.47 - 6.80). ESD showed better en bloc and curative resection rates and local recurrence compared with EMR, but was more time-consuming and had higher rates of bleeding and perforation complications. These results need to be confirmed by high quality trials and further studies in the west. Copyright Georg Thieme Verlag KG Stuttgart. New York.