Background: With the development of endoscopic diagnosis technology, the detection rate of multiple primary gastric cancer is increasing. Aims: To explore the efficacy and safety of endoscopic submucosal dissection (ESD) in the treatment of synchronous multiple primary early gastric cancer (SMPEGC). Methods: Fifteen consecutive patients with SMPEGC treated with ESD from March 2018 to December 2019 at the First Affiliated Hospital of Zhejiang Chinese Medical University were collected. Clinical features and outcomes were retrospectively analyzed. The risk of lymph node metastasis was evaluated according to the eCura system. Results: In 15 patients, 32 lesions were resected and 31 specimens were obtained. Thirteen patients underwent simultaneous resection of multiple primary gastric lesions, and 2 patients underwent staged resection. The operation time of ESD was (138.80±58.06) minutes, the length of hospital stay was (11.47±4.63) days, the lesion diameter was (1.30±1.15) cm, the en bloc resection rate was 100% and the curative resection rate was 71.9%. Postoperative complications occurred in 2 patients. According to the eCura system, the risk of lymph node metastasis was low in the 4 patients with non-curative resection. Three months after the operation, no local residual or recurrence was found in 10 patients. Conclusions: ESD is a feasible choice for the treatment of SMPEGC. The length of hospital stay and overall medical costs can be reduced by resection multiple lesions in one operation. For patients with risk factors of complications, one-time surgical resection should be avoided. The risk of lymph node metastasis is not the same for all the patients with non-curative resection. Maybe the eCura system can better evaluate the risk of lymph node metastasis and provide individualized treatment strategy.