BACKGROUND: Patients with esophageal cancer who receive neoadjuvant chemoradiotherapy are restaged with computed tomography (CT), endoscopic ultrasound with fine needle aspiration (EUS-FNA), and integrated positron emission computed tomography (FDG-PET/CT), and the results affect treatment. METHODS: This is a prospective trial on a consecutive series of patients who had initial chest, abdomen, and pelvis CT scan; EUS-FNA; and fluoro-2-deoxy- d -glucose (FDG)-integrated PET/CT; neoadjuvant chemoradiotherapy; repeat staging tests; pathologic staging; and, if appropriate, resection with lymphadenectomy. The primary objective was to assess the accuracy of these 3 tests in restaging patients after neoadjuvant therapy. RESULTS: There were 48 patients (41 men), and 41 underwent Ivor Lewis esophagogastrectomy with lymphadenectomy. The accuracy of each test for distinguishing pathologic T4 from T1 to T3 disease is 76%, 80%, and 80% for CT scan, EUS-FNA and FDG-PET/CT, respectively. The accuracy for nodal disease was 78%, 78%, and 93% for CT scan, EUS-FNA and FDG-PET/CT, respectively ( P = .04). FDG-PET/CT correctly identified M1b disease in 4 patients, falsely suggested it in 4 patients, and missed it in 2 patients, whereas for CT, it was 3, 3, and 3 patients. Fifteen (31%) patients were complete responders, and FDG-PET/CT accurately predicted complete response in 89% compared with 67% for EUS-FNA ( P = .045) and 71% for CT ( P = .05). CONCLUSIONS: FDG-PET/CT is more accurate than EUS-FNA and CT scan for predicting nodal status and complete responders after neoadjuvant therapy in patients with esophageal cancer. FDG-PET/CT and CT alone provide targets for biopsy, but results are often falsely positive.