Objective: Esophageal endoscopic ultrasound with fine needle aspiration (EUS-FNA) is a critical staging tool for patients with esophageal cancer. Previous reports suggest that it is frequently incorrect when it predicts a patient to be N0. The purpose of this study is to assess the efficacy of EUS-FNA in patients clinically staged N0. Methods: A retrospective cohort study of patients who had a computed tomography scan, EUS-FNA and a positron emission tomography scan prior to undergoing Ivor Lewis esophagogastrectomy with abdominal and thoracic lymphadenectomy. Results: From January 2002 to June 2009, 207 patients underwent Ivor Lewis esophagogastrectomy by one general thoracic surgeon. Ninety-five patients did not undergo neo-adjuvant therapy. Eighty nine of these patients had an EUS-FNA preoperatively and 82 were staged as N0. Seventy-seven (94%) were confirmed as N0 on final pathology (sensitivity 94%, accuracy 95%). Their overall 3-year Kaplan-Meier survival was 68%. Neo-adjuvant chemo-radiotherapy was given to the remaining 112 patients and 107 had a restaging EUS-FNA. Ninety of these patients were staged by EUS as N0. Seventy patients (78%) were N0 on final pathology (sensitivity 82%, accuracy 68%). There was no EUS-FNA-related procedural morbidity or mortality except for sore throat and nausea. Conclusion: EUS-FNA is very accurate and sensitive when it clinically stages patients with esophageal cancer as N0. In addition, it is even accurate and sensitive when restaging patients as N0 after neo-adjuvant chemo-radiotherapy. These results, which differ from previous reports, are critical for guiding treatment decisions. © 2011 European Association for Cardio-Thoracic Surgery.