Over a 14-year period, we observed eight cases of esophagopleural fistula after pneumonectomy for cancer (n = 7) or infectious lung disease (n = 1). In 2 patients, the fistula was probably related to an intraoperative esophageal injury. Two others had mediastinal cancer recurrence, whereas a fistula developed in 4 without any malignancy. Patients presented with empyema, and a contrast swallow procedure disclosed an esophagopleural fistula. Two patients with recurrent cancer were managed conservatively with chest tube insertion and died within 3 months. A patient with chronic empyema had a delayed diagnosis of esophagopleural fistula 2 years after a presumed intraoperative injury; he was managed with thoracoplasty and feeding gastrostomy and died 12 months later. Five patients had an attempt at curative treatment. A single patient underwent thoracoplasty and bipolar exclusion of the esophagus and had secondary reconstruction with a coloplasty; he died with postoperative peritonitis. Four patients underwent thoracoplasty and muscle flap repair of the esophagus. There was 1 operative death from pulmonary embolism, whereas 3 patients recovered and are well with follow-up of 18 months, 2 years, and 5 years, respectively. We conclude that the prognosis of esophagopleural fistula is ominous when associated with cancer recurrence. A curative approach should combine direct repair of the esophagus with a muscle flap and eradication of the associated empyema with thoracoplasty. This aggressive treatment is addressed to debilitated patients and carries high rates of mortality and morbidity.