Objective To observe the short-term efficacy and safety of neoadjuvant sintilimab combined with chemotherapy in the treatment of patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC). MethodsClinical data were collected from patients with locally advanced resectable ESCC who received neoadjuvant immunotherapy combined with chemotherapy followed by surgical treatment at the Thoracic Surgery Department of Jining First People's Hospital from April 2020 to April 2022. The endpoints included major pathological response (MPR), pathological complete response (pCR), R0 resection rate, safety, and postoperative survival. Results A total of 43 patients with ESCC who received at least one cycle of neoadjuvant immunotherapy before surgery were included. Among them, there were 31 males and 12 females, aged from 46 to 77 years, with a median age of 65 years. All patients successfully completed the surgery without any surgical delays. The pCR rate was 14.0% (6/43), the MPR rate was 58.1% (25/43), and the R0 resection rate was 97.7% (42/43). Patients exhibited reliable safety during neoadjuvant therapy and postoperatively. The 2-year overall survival (OS) and disease-free survival (DFS) rates were 90.7% and 81.4%, respectively. Kaplan-Meier survival analysis and log-rank test revealed lower recurrence rates and better survival in the MPR group compared to the non-MPR group. Conclusion The combination of neoadjuvant sintilimab and chemotherapy in the treatment of patients with locally advanced resectable ESCC has demonstrated significant clinical efficacy, while also being safe and reliable.