Objectives: Fever of unknown origin (FUO) is an increasingly accepted indication for PET/CT where it has a relatively high diagnostic yield. This study assesses its diagnostic value for the revised definition of FUO. Methods: The revised definition of FUO is fever of greater than 38.3C for more than 3 weeks duration and an uncertain diagnosis after comprehensive evaluation as an inpatient or outpatient for a minimum of 3 days or 3 outpatient visits, having excluded immunocompromised states. 59 patients (pts) (F=35, age 18-92) with this definition underwent PET with full diagnostic contrast enhanced CT. The value of PET/CT in determining the underlying etiology of FUO was retrospectively evaluated by comparing the study findings with a final diagnosis. Final diagnosis was formulated by 6 month clinical, imaging, microbiological and histopathological follow up. When no cause was found by follow up, the negative study was considered a true negative. Results: Final diagnosis was made in 35/59 pts. Diagnosis was reached in 86% of these pts with an abnormal study but only in 14% of pts with a normal study. Underlying etiologies included vasculitides (14 pts), infectious foci (14 pts), neoplasm (6 pts) and drug fever (1 pt). Before ordering a PET/CT, conventional CT or MRI was performed in 43 pts. We considered that a PET/CT was essential to establish the final diagnosis in 15/43 pts (35%) with inconclusive CT or MRI. Conclusions: 18F-FDG PET/CT contributed to establishing a final diagnosis in 64% of 47 pts with positive PET/CT findings and in 39% of all pts with the revised definition of FUO.