EUS-derived maximum tumor thickness (MTT) pre- and post-neoadjuvant chemoradiotherapy (NCRT) for locally advanced esophageal squamous cell carcinoma (LA-ESCC) indicates treatment response. However, the accuracy of predicting long-term survival remains uncertain. This study aimed to investigate the association between EUS-derived MTT pre- and post-NCRT and tumor shrinkage rate as well as long-term survival in patients with LA-ESCC receiving NCRT.We retrospectively enrolled patients with LA-ESCC who underwent EUS examination from 2017 to 2021. Tumor shrinkage rate was the ratio of the difference between pre- and post-MTT to pre-MTT. The most fitted cutoff values were determined by the receiver operating characteristic curve. Univariate and multivariate Cox regression analyses and Kaplan-Meier curves were used to calculate overall survival (OS) and progression-free survival. Data from another center were also used for external validation testing.Two hundred thirty patients were enrolled. Of the patients, 178 completed the first EUS pre-NCRT and obtained pre-MTT, 200 completed the reexamined EUS post-NCRT and obtained post-MTT, and 148 completed both EUS and achieved tumor shrinkage. For all the patients, the 1- and 3-year OS rates were 93.9% and 67.9%, and progression-free survival rates were 77.7% and 54.1%, respectively. The median follow-up period was 30.6 months. Thinner post-MTT (≤8.8 mm) and EUS responder (tumor shrinkage rate ≥52%) were independently associated with better OS.EUS-derived MTT and tumor shrinkage post-NCRT are independent prognostic factors for long-term survival and may be an alternative method for evaluating tumor response in patients with LA-ESCC after NCRT.Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc on behalf of Scholar Media Publishing.