Abstract Background Induction therapy followed by conversion surgery is potentially curative for locoregionally unresectable esophageal squamous cell carcinoma (ESCC). However, the optimal induction treatment strategy is unclear. The study aimed to evaluate the feasibility and efficacy of cisplatin, paclitaxel and immune checkpoint inhibitors as conversion therapy for locoregionally unresectable ESCC. Methods Clinicopathological variables of cT4b ESCC patients who received neoadjuvant chemoimmunotherapy were retrieved from the prospective database of the Surgical Esophageal Cancer Patient Registry in West China Hospital, Sichuan University. Enhanced computed tomography, ultrasonography and bronchoscopy were routinely used for the diagnosis. The treatment protocol of neoadjuvant chemoimmunotherapy included 2 cycles of immunotherapy plus chemotherapy with the interval of 3 weeks among each cycle. All patients received 2 cycles of Pembrolizumab (200 mg, D1), Sintilimab (200 mg, D1), Tislelizumab (200 mg, D1) or Camrelizumab (200 mg, D1) intravenously. Concurrently all patients received 2 cycles of cisplatin (75 mg/m2 of body-surface area, D1) and paclitaxel (175 mg/m2 body-surface area, D1) intravenously. The perioperative parameters and short-term surgical outcomes were presented (Table). Results Between January 2020 and December 2022, a total of 317 ESCC patients who underwent neoadjuvant chemoimmunotherapy followed by surgery were screened. Twenty cT4b patients with middle or upper thoracic ESCC were finally enrolled in this study. Pretreatment tumor invades the trachea (4, 20%), left main bronchus (16, 80%), and aorta (6, 30%), respectively. All the patients were successfully performed by McKeown minimally invasive esophagectomy except for one patient conversion to thoracotomy. R0 resection was achieved in 15 patients, 4 patients underwent R1 resection and 1 patient underwent R2 resection. Mean operation duration was 290.4 ± 57.5 min. Mean estimated blood loss was 94.4 ± 108.8 ml. Three patients had postoperative pneumonia, two patients had postoperative pleural effusion and one patient had postoperative recurrent laryngeal nerve paralysis. No patient had postoperative anastomotic leak. No postoperative reoperation was needed and there was no perioperative mortality. Mean length of hospital stay was 10.9±1.4 days. 90-day mortality occurred in one patient with postoperative multiple systemic metastasis. Fifteen patients are alive with a median follow up of 18 months. One patient died with regional lymph node recurrence and three patients died with hematogenous dissemination. Conclusion Multimodal treatment strategy combining immunotherapy and chemotherapy may convert unresectable tumors into potentially operable ones, and achieved favorable survival. Longer follow-up and larger sample size are needed to verify our preliminary results.