Objective To investigate the risk factors for synchronous multiple early gastric cancer (SMEGC). Methods A retrospective analysis was conducted on data of 390 patients with early gastric cancer, including 353 cases of solitary early gastric cancer (SEGC group) and 37 cases of SMEGC (SMEGC group), who underwent endoscopic submucosal dissection (ESD) in Chinese PLA General Hospital from January 2017 to June 2019. The differences in clinical characteristics (gender, age, body mass index, smoking status, drinking status, family history of gastrointestinal cancer and other cancers, etc.) and pathological characteristics (size, location, morphology, differentiation degree, invasion depth, with or without Helicobacter pylori infection, intestinal metaplasia, ulcers and atrophic gastritis of lesions, etc.) between the two groups were compared by t test, Mann-Whitney U test, Chi-square test, or Fisher's exact test. Logistic regression (forward LR) was used to screen the independent risk factors for SMEGC. Results There were no significant differences in the general clinical characteristics between SMEGC group and SEGC group (P>0.05). Significant statistical differences were observed in the location of lesions (χ2=8.375, P=0.015), the proportion of atrophic gastritis [48.6% (18/37) VS 23.8% (84/353), χ2=10.710, P=0.001] and the proportion of intestinal metaplasia [81.1% (30/37) VS 43.1% (152/353), χ2=19.452, P<0.001] between the two groups, but there were no significant differences in other pathological characteristics (P>0.05). Multivariate logistic regression analysis showed that location of lesions in the middle 1/3 of stomach (VS upper 1/3: P=0.036, OR=3.38, 95%CI: 1.08-10.53), in the lower 1/3 of stomach (VS upper 1/3: P=0.049, OR=2.59, 95%CI: 1.00-6.69), presence of intestinal metaplasia (P=0.001, OR=4.38, 95%CI: 1.77-10.86) and atrophic gastritis (P=0.043, OR=2.24, 95%CI: 1.04-5.07) were independent risk factors for SMEGC. Conclusion Patients with early gastric cancer located in the middle or lower 1/3 of stomach, with intestinal metaplasia and atrophic gastritis are prone to SMEGC and should be carefully evaluated and closely followed up after ESD.