Due to the increasing use of minimally invasive techniques, some authors have questioned the necessity to dissect the azygos vein as part of the en-bloc esophagectomy in patients with esophageal cancer. This study investigates the nodal clearance associated with resection of the azygos vein. Ninety-two patients with esophageal carcinoma were included in this prospective analysis. In all patients, a standard transthoracic en-bloc esophagectomy was performed including the resection of the azygos vein from the superior vena cava to the level of the diaphragm. After resection, the azygos vein with its adjacent connective tissue was separated from the tubular esophagus. The separated azygos vein specimen was histopathologically examined for the presence of lymph nodes (LN) and possible nodal metastasis. A total of 2,778 LN with a mean of 30.2 LN for each patient were resected. In 60 patients, 216 of 1,666 mediastinal LN (13.0%) were located along the azygos vein. Seven of 39 pN1 patients (17.9%) had LN metastases in the separated azygos vein specimen. In these seven patients, a total of 23 metastatic nodes were detected along the azygos vein. LN metastases along the azygos vein are too frequent to neglect their existence. Therefore, standard en-bloc esophagectomy including dissection of the azygos vein should not be abandoned irrespective of the surgical approach.