The use of the stomach as an esophageal substitute has become a well-established treatment procedure after esophagectomy for cancer. During the procedure, a bilateral truncal vagotomy is performed, which should prevent the occurrence of acid-related diseases in the gastric tube and in the remaining esophagus. We report the case of a man who presented a plugged perforated peptic ulcer that subsequently decompensated following endoscopic examination 1 year after a transthoracic esophagectomy with neoadjuvant chemo-radiation for a middle third squamous cell carcinoma. Resection of the ulcer and suture with a pleural patch was performed. There was no evidence of recurrent malignancy at time of surgery. The pathophysiology of gastric tube ulcer is multifactorial. Long-term treatment with an anti-secretory proton pump inhibitor may decrease esophageal complications of duodeno-gastric-esophageal reflux and could prevent the recurrence of gastric tube ulcers.