UNLABELLED In a group of oncologic patients undergoing (18)F-FDG PET/CT, we compared 4 different protocols of hydration to investigate their impact on image quality and to choose the best practice. METHODS One hundred twenty subjects undergoing (18)F-FDG PET/CT were randomized into 4 groups: group A, receiving free oral hydration; group B, receiving an intravenous injection of 10 mg of furosemide and infusion of 500 mL of saline solution starting 5 min after tracer injection; group C, receiving oral hydration with 500 mL of water; and group D, receiving intravenous injection of 10 mg of furosemide and infusion of 250 mL of the saline solution starting 30 min after the (18)F-FDG injection. The maximum standardized uptake value of muscular and adipose tissues, blood pool (aortic and left ventricular cavity), bladder, and renal parenchyma was calculated for each subject. RESULTS These 4 groups were comparable in age, body mass index, blood glucose level, and serum creatinine level. Group A showed the worst results. The controlled hydration protocols (groups B, C, and D) provided lower background activity in the soft tissues and lower urinary activity in the bladder and kidney without significant differences in blood activity. The administration of furosemide produces lower activity in the urinary tract without significant changes in (18)F-FDG distribution in the muscle, fat, or blood pool. The best results were in group D. CONCLUSION Controlled hydration, particularly with standardized parenteral protocols, reduces the background activity in the soft tissues with the potential benefit of increasing the tumor-to-background contrast. Furosemide does not change tracer distribution in normal tissues but improves the quality of PET/CT images, reducing activity in the excretory system, particularly if the furosemide is administered late after (18)F-FDG injection.