BACKGROUND: Neoadjuvant chemoradiotherapy (NCRT) combined with surgery is the standard treatment option for patients with locally advanced esophageal squamous cell carcinoma (ESCC). However, whether adjuvant chemotherapy (AC) administered postoperatively has a survival benefit remains inconclusive. OBJECTIVES: To investigate whether AC is necessary after NCRT and esophagectomy and determine which patients might benefit from it. DESIGN: A retrospective study. METHODS: This retrospective study examined patients with ESCC treated with NCRT followed by radical esophagectomy at three hospitals between March 2016 and December 2022. Patients were assigned into the adjuvant and non-adjuvant therapy groups based on whether they received postoperative AC, allowing the comparison of disease-free survival (DFS) and overall survival (OS) between the two groups. In addition, based on whether postoperative pathology indicated pathological complete response (pCR), patients were classified into the pCR and non-pCR populations, with DFS and OS separately analyzed for each subgroup. RESULTS: Overall, 218 eligible patients were enrolled. No significant advantage was found in DFS ( CONCLUSION: In the real world, patients with ESCC who underwent NCRT combined with radical esophagectomy and whose postoperative pathology was pCR did not benefit from AC. However, AC significantly improved DFS and OS in patients whose postoperative pathology did not reach pCR.