Neoadjuvant chemotherapy (nCT) and chemoradiotherapy (nCRT) are the standard treatments in patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC). Adding PD-1 inhibitor to the chemotherapy has shown significant clinical benefits in first-line treatment of advanced ESCC. This study evaluated the efficacy and safety of neoadjuvant sintilimab plus chemotherapy in patients with resectable locally advanced ESCC.The clinical data of 96 patients with resectable locally advanced ESCC, treated with sintilimab plus chemotherapy followed by esophagectomy, were reviewed. The pathologic complete response (pCR) rate, major pathological response (MPR) rate, R0 resection rate, tumor downstaging, survival, and safety were retrospectively analyzed.Patients were between the ages of 43 and 78 years (interquartile range [IQR], 60-69 years). Forty (41.7%) were diagnosed with stage II ESCC, 52 (54.2%) with stage III, and 4 (4.2%) with stage IVA. Sixty-seven (69.8%) were male, and 84 (87.5%) patients had an ECOG PS of ≤1. Forty-eight (50.0%) patients received 3-4 cycles of the neoadjuvant treatment. Twenty-nine (30.2%) patients obtained pCR, and MPR was achieved in 60 (62.5%) patients. The R0 resection rate was 99%. Eighty (83.3%) patients achieved clinical downstaging, and 71 (74.0%) achieved pathological downstaging. The median follow-up was 8.9 months, and 1-year DFS rate was 95.2% (95% CI, 88.8%-100%). Grade 3-4 TRAEs occurred in 12 (12.5%) patients, and the incidence of grade 3-4 surgical complications was 2.1%. No deaths were reported.These real-world data revealed that neoadjuvant sintilimab plus chemotherapy could provide encouraging pCR with good tolerability for resectable locally advanced ESCC, and this regimen warrants further exploration in prospective clinical studies.Copyright © 2022 Lv, Tian, Li, Huang, Sun, Gai, Li and Tian.