To clarify whether systemic lymph node dissection (LND) influences the safety of surgery and the survival of patients with locally advanced esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemoradiotherapy (nCRT). Prognostic impact of systemic lymphadenectomy during surgery after nCRT for ESCC is still uncertain and requires clarification. This is a secondary analysis of NEOCRTEC5010 trial which compared nCRT followed by surgery versus surgery alone for locally advanced ESCC. Relationship between number of LND and perioperative, recurrence and survival outcomes were analyzed in the nCRT group. Three-year overall survival was significantly better in the nCRT group than the S group (75.2% vs 61.5%; P=0.011). In the nCRT group, greater number of LND was associated with significantly better overall survival (HR, 0.358; P < 0.001) and disease-free survival (HR, 0.415; P=0.001), but without any negative impact on postoperative complications. Less LND (< 20 vs ≥ 20) was significantly associated with increased local recurrence (18.8% vs 5.2%, P=0.004) and total recurrence rates (41.2% vs 25.8%, P=0.027). Compared to patients with persistent nodal disease, significantly better survival was seen in patients with complete response and with LND ≥ 20, but not in those with LND < 20. Systemic lymph node dissection does not increase surgical risks after nCRT in ESCC patients. And it is associated with better survival and local disease control. Therefore, systemic lymphadenectomy should still be considered as an integrated part of surgery after nCRT for ESCC. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.