Background: Neoadjuvant chemotherapy or chemoradiotherapy followed by surgery is the standard of care for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, recurrence post-surgery remains a concern. Recent single-arm studies with neoadjuvant camrelizumab plus chemotherapy showed promising results. This multicenter, randomized, open-label, phase III study aims to evaluate the role of neoadjuvant camrelizumab plus chemotherapy followed by adjuvant camrelizumab, versus neoadjuvant chemotherapy alone for resectable LA-ESCC. Methods: Patients with resectable thoracic LA-ESCC (T1b-3N1-3M0 or T3N0M0) were stratified according to clinical stage (I/II, III, or IVa) and randomized (1:1:1) to three groups for two 3-week cycles of neoadjuvant therapy. Group A received camrelizumab, albumin-bound paclitaxel and cisplatin; group B used camrelizumab, paclitaxel and cisplatin; group C received paclitaxel and cisplatin. Surgery was planned 4-6 weeks post-neoadjuvant therapy. Postoperative adjuvant camrelizumab every 3 weeks was given to groups A and B for up to 15 cycles. The co-primary endpoints were pathological complete response (pCR) rate, assessed by an independent blinded pathological committee, and event-free survival, evaluated by investigators per RECIST 1.1. The overall type I error was controlled at a one-sided 0.025 across the primary endpoints using a graphical method. Results: Between April, 2021, and August, 2023, we enrolled 391 patients: group A (n = 132), group B (n = 130), and group C (n = 129). 106 (27.1%), 279 (71.4%), 6 (1.5%) patients were in clinical stage I/II, III, and IVa. Tumors were located in the upper, middle, and lower thoracic esophagus for 41 (10.5%), 201 (51.4%), and 149 (38.1%) patients. 128 (97.0%), 125 (96.2%), and 122 (94.6%) patients from groups A, B, and C completed two cycles of neoadjuvant therapy, and 114 (86.4%), 116 (89.2%), and 103 (79.8%) underwent surgery. In the intention-to-treat population, the pCR rate was significantly higher in groups A (28.0%) and B (15.4%) compared to group C (4.7%) (group A vs. C: difference, 23.5%, 95%CI, 15.1-32.0; OR, 8.11, 95%CI, 3.28-20.06; two-sided P < 0.0001; group B vs. C: difference, 10.9%, 95%CI, 3.7-18.1; OR, 3.81, 95%CI, 1.48-9.80; two-sided P = 0.0034); major pathologic response rates were 59.1%, 36.2%, 20.9% for groups A, B and C. In the surgical set, the R0 resection rate was 99.1%, 95.7% and 92.2% for groups A, B and C, and the incidence of postoperative complications was 34.2%, 38.8% and 32.0%. During neoadjuvant treatment, the incidence of grade ≥3 treatment-related adverse events was 34.1%, 28.5% and 28.8%. Conclusions: In resectable LA-ESCC patients, neoadjuvant camrelizumab with chemotherapy showed superior pCR and a tolerable safety profile compared to neoadjuvant chemotherapy alone. Clinical trial information: ChiCTR2000040034.