Background: The ideal time to repeat a 2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) scan to accurately restage a patient after neoadjuvant chemoradiotherapy for non-small cell lung cancer (NSCLC) is unknown. Methods: This retrospective cohort study used a prospective database of patients who underwent neoadjuvant chemoradiotherapy, an initial and repeat FDG-PET/CT scan, and pathologic staging. The accuracy of the clinical stage suggested by repeat FDG-PET/CT was compared with the actual pathologic stage. Receiver operating characteristic (ROC) curves were used to determine when it was most accurate to repeat the FDG-PET/CT after the completion of the last dose of chest radiation. Results: The study comprised 109 patients, 93 of whom patients received 60 Gy (or higher) of radiotherapy. The median time to restaging was 24 days (range, 2 to 88 days). ROC analysis showed the optimal time to restage patients was 26 days for overall staging (area under the curve [AUC], 0.88) and 29 days for N2 restaging (AUC, 0.82). The accuracy for overall stage was 3 (38%) of 8 for patients for less than 10 days, 28 (72%) of 39 for patients between 11 and 20 days, 42 (88%) of 49 between 21 and 30 days, and 8 (62%) of 13 for 31 days or more. The accuracy for these time intervals for the restaging of the N2 lymph node was 50% (1/2) 40% (2/5), 88% (7/8), and 100% (3/3), respectively. Conclusions: The optimal time to perform a repeat FDG-PET/CT scan after the completion of neoadjuvant chemotherapy and high-dose radiotherapy to maximize its accuracy for restaging patients with NSCLC is about 1 month after the last dose of radiation. © 2007 The Society of Thoracic Surgeons.