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BACKGROUND Esophagopleural fistula (EPF) is a rare but life-threatening complication following pneumonectomy, with a reported incidence of up to 1% and a mortality rate ranging from 49% to 63%. Management strategies vary depending on the fistula's characteristics and the patient's clinical status, encompassing conservative, endoscopic, and surgical approaches. CASE REPORT We report the case of a 65-year-old woman diagnosed with lung adenocarcinoma and N2 nodal involvement who received neoadjuvant chemo-immunotherapy, followed by surgical treatment with left pneumonectomy. In the early postoperative course, she developed fever and pleural contamination with food particles, leading to the diagnosis of EPF via methylene blue test and esophagogastroduodenoscopy (EGD). Initial endoscopic treatment with stent placement was attempted multiple times but its failure prompted the need for surgical intervention. After addressing the infectious and nutritional issues associated with the condition and optimization of the patient's clinical status, a complex 3-stage procedure was performed involving esophageal exclusion and reconstruction of the gastrointestinal tract using a retrosternally transposed gastric conduit. This was achieved through 3 surgical approaches: laparoscopy, left cervicotomy, and minilaparotomy. The postoperative course was uneventful, with successful reintroduction of oral intake. The esophagogram performed 3 months postoperatively showed a good caliber of the esophagogastric anastomosis and no leakage of contrast from the esophageal lumen. CONCLUSIONS Surgical treatment of large esophagopleural fistulas is indicated when endoscopic treatment fails. Furthermore, esophageal exclusion and bypass is the best course of action when the extent of the fistulous tract presents a problem for direct repair and the chest cavity presents difficulties.