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This study aimed to prospectively investigate 18F-FDG PET/CT role for the assessment of sarcoidosis activity and extension in comparison with thoracic high-resolution CT (HRCT) and to evaluate the potential clinical impact of PET/CT findings. Secondary aim was to investigate the changes in cardiac FDG uptake related to the specific preparation before PET/CT.We prospectively enrolled biopsy proven sarcoidosis patients consecutively referred for 18F-FDG PET/CT since January 2010. PET/CT was performed after a fat meal followed by 12-hour fasting and compared with thoracic HRCT results obtained in supine position and clinical follow-up. The impact on the clinical management was recorded.Patterns of cardiac FDG uptake of the study group were compared with a historical population in which PET/CT was performed following standard preparation.A total of 28 patients were enrolled, and 35 PET/CT scans were reviewed. On a scan basis, PET/CT was concordant with HRCT in 16 (45.7%), detecting active disease in 10/16 and no signs of activity in 4/16. PET/CT data had a direct impact on management in 4/16.In 19 (54.3%) discordant scans, PET/CT finding was positive in 14 and negative in 5. PET/CT findings influenced the clinical management in 18/19 cases.Considering all scans, PET/CT information influenced the clinical management of 22 (63%) of 35.Our data suggest that cardiac FDG uptake may vary regardless of the preparation before PET/CT.18F-FDG PET/CT was useful to assess sarcoidosis activity and extension and provided valuable information for the clinical management in a single-step examination. Additional data are needed to better ascertain the optimal patient preparation before image acquisition to improve sensitivity of heart lesions.