Objective To evaluate the efficacy and prognosis of endoscopic submucosal dissection (ESD) for undifferentiated-type early gastric cancer (EGC). Methods Data of 393 patients with 400 EGC lesions who underwent ESD between January 2010 and April 2019 in the First Affiliated Hospital of Nanjing Medical University were collected in the retrospective study. Patients were divided into undifferentiated-type group (50 cases with 50 lesions) and differentiated-type group (343 cases with 350 lesions) according to postoperative pathology. Their data including age, gender, size and location of the resected lesion, general classification, depth of infiltration, presence or absence of ulcers, and follow-up were compared. Results Logistic regression analysis showed that age ≤60 years (OR=2.02, 95%CI: 1.04-3.95, P=0.011), female (OR=2.83, 95%CI: 1.41-5.68, P=0.003), gastric antrum lesions (OR=3.92, 95%CI: 1.65-9.30, P=0.002), endoscopic depressed type (OR=5.37, 95%CI: 2.16-13.38, P<0.001), and submucosa invasive depth (OR=5.09, 95%CI: 2.40-10.80, P<0.001) were independent risk factors for undifferentiated EGC. The undifferentiated-type group showed a significantly higher non-curative resection rate [90.0% (45/50) VS 19.8% (68/343), χ2=104.902, P<0.001]. Of the 393 patients, 5(4.4%) died in the 113 patients with non-curative resection, while 2 (0.7%) died in the 280 patients with curative resection. Patients with non-curative resection had a higher mortality (χ2=5.558, P=0.023). There were 27 and 51 patients undergoing additional surgery in the undifferentiated-type group and the differentiated-type group, respectively. None of them had recurrence. Among the 315 patients who did not undergo surgery, the recurrence rate of the undifferentiated-type group was significantly higher than that of the differentiated-type group [26.1% (6/23) VS 4.1% (12/292), χ2=5.560, P<0.001]. Conclusion Young age (≤60 years), female, gastric antrum lesions, endoscopic depressed type, and submucosa invasive depth are predictors of undifferentiated EGC. Patients with undifferentiated EGC have a higher non-curative resection rate and higher possibility of recurrence after ESD, and additional operation are suggested.