BackgroundMultimodal therapy regimens became the standard of care for patients with esophageal cancer, whereas surgical resection remains at the center of curative treatment modalities. Current guidelines provide no recommendations on the extent of the oral resection margin, especially in the era of neoadjuvant therapy. Therefore, this study aimed to evaluate the relationship between the oral tumor-free resection margin and overall survival. MethodsRetrospective study with 382 1:1 propensity-matched patients out of 660 patients, operated between 2013 and 2019, with an Ivor-Lewis-esophagectomy for adenocarcinoma and squamous cell carcinoma of the esophagus or esophagogastric junction after neoadjuvant therapy. Independent pathologists measured the oral resection margin after formalin fixation. ResultsThe mean oral tumor-free resection margin was 37.2 ± 0.6 mm. The ideal cut-off for survival differences was determined for 33 mm. Patients with an oral resection margin of more than 33 mm had a better median overall survival (≤33 mm: 45.0 months, 95% confidence interval: 22.4–67.6 months, >33 mm: not reached, P = .005). An oral resection margin of more than 33 mm proved to be an independent favorable prognostic factor for patients' overall survival in multivariate Cox regression analyses (P = .049). ConclusionThis study analyzed a patient cohort retrospectively after curative intended Ivor-Lewis-esophagectomy after neoadjuvant therapy. An oral resection margin of more than 33 mm is a factor for improved overall survival. Therefore, a minimum resection margin of 34 mm after fixation could be suggested.