Background: As indication for endoscopic resection for gastric neoplasms have been expanded, patients receiving multiple times of endoscopic resection for metachronous or synchronous lesions have been increasing. We aimed to compare clinicopathologic characteristics of patient with gastric neoplasm in a single location and multifocal lesions of three or more. Methods: From January 2006 to December 2021, 255 patients underwent endoscopic resection for three or more of multifocal lesions at tertiary medical institution were reviewed retrospectively and 8667 patient showed no recurrence after endoscopic resection for single lesion. The clinicopathologic characteristics of index gastric lesions were compared. Results: The male ratio was higher in multifocal lesions group than single lesion group (83.9% vs. 68.4%, P < 0.001). Diabetes mellitus was significantly more in multifocal lesions group than single lesion group (20.4% vs. 18.4%, P = 0.046), however hypertension, cardiovascular disease, kidney disease, and hepatitis showed no significant difference between the two groups. Smoking rate was significantly higher in the multifocal lesions group (current smoker 31.0% vs. 25.4%, and ex-smoker 24.7% vs. 24.8%, P = 0.028). In rapid urease test for Helicobacter pylori infection, the multifocal group showed significantly higher positives (54.9% vs. 40.8%, P < 0.001). Tumor depth, lymphovascular invasion, and perineural invasion showed no significant differences. Conclusions: Patients with multifocal early gastric neoplasms showed higher male ratio, higher rate of diabetes mellitus, and smoking rate compared with single lesion group. In addition, Helicobacter pylori infection was also significantly higher in patients with multifocal gastric neoplasm.