Purpose: The aim of this study was to evaluate the role of 18F-FDG PET/CT performed after surgery but before radioiodine therapy in patientswith differentiated thyroid cancer. Procedures: FDGPET/CTwas performed off L-thyroxine in 60 newly diagnosed differentiated thyroid cancer patients. Clinical and hematological evaluation as well as high-resolution neck ultrasound were performed. All patients underwent a complete follow-up (range, 6-67 months; mean [SD], 31.7 [20.6] months). The date of recurrence or the most recent office visit was recorded. Progression-free survival (PFS) is the primary end point of this study. Analysis was performed by Cox proportional hazards model. Survival curves were generated using Kaplan-Meier estimates, and the log-rank test was used to assess significance. Results: FDG PET/CTwas negative in 63% of patients, 20% had FDG thyroid bed uptake, 5% distantmetastases, and 12% lymph node FDG uptake. In patients with positive FDG PET/CT scan (ie, thosewith distant metastases or lymph node uptake), a higher rate of recurrence was observed (50% vs 6%, P < 0.05). Thyroglobulin, neck ultrasound, stage, and FDGPET/CT correlatedwith PFS at univariate analysis. At multivariate analysis, only thyroglobulin and FDG PET/CT continued to be predictors of PFS. Patients with a negative FDG PET/CT scan have a better PFS either in thewhole group or in thosewith elevated thyroglobulin level (both >2 ng/mL and >10 ng/mL). Conclusions: FDG PET/CTwas abnormal in 17% of patients. Moreover, FDG PET/CT has an independent prognostic role, with a better PFS in patients with a negative scan.