Objective: To compare the diagnostic ability and time efficiency of contrast-enhanced (CE) whole body fluorodeoxyglucose (FDG) positron emission tomography/magnetic resonance imaging (PET/MRI) protocol and non-CE (NCE) protocol. Subjects and Methods: Ninety-three patients with known primary tumors underwent whole-body hybrid FDG PET/MRI during the follow-up of their malignancies with the use of NCE and CE protocols. The NCE PET/MRI protocol consisted of diffusion-weighted (b = 0 and 800 s/mm(2)) and T1-weighted Turbo Flash in the axial plane and T2-weighted HASTE sequence in the coronal planes (sigma = 25 min). The CE PET/MRI protocol was performed by acquiring axial serial CE 3D FS VIBE images in the upper abdomen, completing the whole body in the late phase in the axial plane (sigma = 30 min). Results: There was a statistically significant difference between the total number of lesions detected by the CE protocol (median 2, interquartile range (IQR) 0-14) and that detected by the NCE protocol (median 1, IQR 0-5; p < 0.001). More malignancies were detected in the abdomen (p < 0.001) and brain (p < 0.001) with the CE PET/MRI protocol, whereas no significant difference was present when comparing the 2 protocols in the detection of malignancies in the head and neck (p = 0.356), thorax (p = 0.09), lymph nodes (p = 0.196), and bone (p = 0.414). Conclusion: The CE FDG PET/MRI protocol enables fast and accurate detection of malignancies compared to the NCE FDG PET/MRI protocol, particularly in the upper abdomen and brain. Diagnostic ability and time efficiency can be increased with the proposed short CE protocol in place of the whole body PET/MRI protocol including both NCE and CE imaging sequences.