Endoscopic submucosal dissection (ESD) is a standard treatment for early stage esophageal neoplasia. However, because the residual mucosa after ESD retains a high potential for development of metachronous neoplasia, recurrence sometimes develops proximal to a previous ESD scar. Such lesions are predictably difficult to treat with ESD due to severe submucosal fibrosis. In the absence of prior reports, we evaluated the clinical outcomes of esophageal neoplasia located proximal to a previous ESD scar. This was a retrospective observational study in a single institution. Between May 2004 and March 2016, 549 consecutive patients with 927 esophageal lesions were treated with ESD. The initial or largest lesion was the target in patients with multiple lesions. The primary treatment outcomes were resectability and adverse events of esophageal neoplasia located proximal to a previous ESD scar (recurrent group). These patients were compared with cases of primary esophageal ESD (primary group). Secondary outcomes were factors predictive of esophageal perforation. Perforation was defined as a visible hole in the esophageal wall, exposing the mediastinal space. Multivariate logistic regression and the generalized estimating equation were used for statistical analysis, and inverse probability of treatment weighting (IPTW) with propensity scores was used to reduce selection bias between the groups. A total of 545 primary cases and 29 recurrent cases were evaluated. Age, antithrombotic use, macroscopic appearance, lesion size, clinical invasion depth, and treatment device significantly differed between the groups. En bloc and complete (R0) resection rates in the recurrent group were lower than those in the primary group (79.3% vs. 98.3%, p<0.01 and 75.9% vs. 93.4%, p<0.01). Perforations occurred more frequently in the recurrent group than in the primary group (10.3% vs. 2.0%, p=0.03). However, these could be treated with endoscopic closure and conservative management. Rates of delayed bleeding and stricture were similar between the groups. A lesion located proximal to a previous esophageal ESD scar was an independent predictive factor for perforation, following adjustment for lesion size and circumference using multivariate logistic regression analysis (odds ratio (OR)=10.37, 95% confidence interval (CI): 2.15-49.94, p=0.004). IPTW methods showed similar results (OR=6.78, 95% CI: 1.40-32.98, p=0.018). Limitations of this study were the small sample size and data from a single center. ESD for esophageal neoplasia located proximal to a previous ESD scar was difficult to completely resect and increased the likelihood of perforation. Large centers with surgeons specialized in treating the esophagus may be recommended for ESD of such lesions.