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Backgrounds: Endoscopic submucosal dissection (ESD) has been widely performed in the treatment of early esophageal squamous cell carcinoma (ESCC). Few studies have compared the long-term outcomes of esophageal ESD based on absolute indications and relative indications. The aim of the current study was to investigate the safety and efficacy of ESD for early ESCC with relative indications., Methods: 297 patients with early ESCC who underwent ESD were retrospectively analyzed. They were divided into 3 groups: group A, the absolute indications group; group B, the relative indications without additional treatment after ESD group; and group C, the relative indications with additional treatment after ESD group. The baseline characteristics, therapeutic efficacy, complications, prognosis outcomes, and follow-up data were evaluated., Results: During the median follow-up period of 51.0 months (range 6-101 months), the incidence of local recurrence in groups A, B, and C was 1.63% (3/184), 4.23% (3/71), and 0 (0/42), respectively (p = 0.253). The 5-year overall survival rates were 97.83% (95% CI: 95.69-99.95%) in group A, 95.77% (95% CI: 90.95-100.00%) in group B, and 97.62% (95% CI: 92.81-100.00%) in group C with no significant differences among these 3 groups., Conclusions: ESD is a feasible and effective treatment for early ESCC with relative indications. Under the premise of sufficient preoperative assessment and scheduled postoperative endoscopic surveillance, additional treatment might not be necessary for patients with relative indications after ESD procedures., (© 2020 S. Karger AG, Basel.)