Objective To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) in the treatment of ileocecal valve (ICV) lipoma. Methods Retrospectively analyzed 59 patients with ileocecal lipoma who underwent ESD treatment from December 2013 to June 2023 in the Endoscopy Center of Zhongshan Hospital, Fudan University. According to the location of the lesion, the patients were divided into ileocecal valve group and cecum group. The operation time, operation speed, en bloc resection rate, and complications between the two groups were compared. Results A total of 59 patients with ileocecal lipoma were enrolled, including 31 patients in the ileocecal flap group and 28 patients in the cecum group.There were no significant differences in gender, age, specimen size, lesion size, en bloc resection rate between the two groups. Lipomas in both the ileocecal valve group and the cecum group were successfully resected by ESD. The en bloc resection rates were 100% (31/31) and 92.8%(26/28) respectively,and the difference was not statistically significant (χ2 =0.033, P=0.133). The median operation time was 26 minutes in the ileocecal valve group and 20 minutes in the cecum group, and the difference was statistically significant (Z=-0.136, P=0.027). The median operation speed was 0.14 cm2/min in the ileocecal valve group and 0.24 cm2/min in the cecum group, and the difference was statistically significant (Z=-0.223, P=0.022). No intraoperative bleeding or perforation occurred and only one fever occurred in the ileocecal valve group after surgery. During the median follow-up of 38 (7-106) months, there was no case of residual tumor or recurrence. Conclusion Although ESD of ileocecal valve lipoma has certain surgical difficulties, it is still a safe, feasible and effective treatment method.