Treatment strategies for head and neck cancer strongly depend on eventual tumor resectability. Besides factors defining T4b stage, such as invasion of the mediastinum, invasion of the prevertebral space and vascular encasement or invasion, tumor resectability also depends on several other factors. Head and neck cancer is supposed to be one field where PET/MR might offer benefits over PET/CT, particularly with regard to local tumor invasion. However, specific data about the imaging assessment of tumor resectability with PET/MR are currently lacking. The purpose of this prospective study was to compare the diagnostic accuracy of contrast-enhanced PET/MR with that of contrast-enhanced PET/CT in the assessment of tumor resectability in patients with head and neck cancer.This prospective study was approved by the institutional review board and by national government authorities. Sequential contrast-enhanced PET/CT-MR was performed in 175 patients (133 males, median age 65 years, range 24 – 91 years) referred for the staging or re-staging of head and neck cancer. Tumors were assessed with PET/CT and PET/MR for the presence of resectability-defining factors: T4b status (mediastinal invasion, invasion of the prevertebral space, vascular encasement), and another eight findings that would imply obstacles for surgical removal (invasion of the laryngeal cartilage, invasion of the pre-epiglottic fat pad, perineural spread, orbital invasion, bone infiltration, skull base invasion, dural infiltration, invasion of the brachial plexus).One hundred seventy five patients referred for the initial staging (n = 31) or re-staging (n = 144) of head and neck cancer underwent PET/CT-MR imaging. One hundred seventeen patients were excluded subsequently due to absence of tumor on both clinical examination and imaging. According to the standard of reference, 30 (52%) of the remaining 58 patients were diagnosed as resectable (20 patients were confirmed by histopathological findings, the other 10 patients were confirmed by imaging and clinical findings). The remaining 28 patients (48%) were diagnosed as not resectable (10 patients were confirmed by intraoperative and histopathological findings, the other 18 patients were confirmed by imaging and clinical findings). In these 28 patients diagnosed as not resectable, 62 lesions with a potential impact on resectability were found, thereof 15 T4b-defining factors and 47 other factors. Overall, the sensitivity/specificity/accuracy of resectability-defining factors of PET/CT and PET/MR was 0.919/0.990/0.983 and 0.984/0.993/0.992 (p = 0.727), respectively, per lesion, and 0.964/0.867/0.914 and 0.964/0.900/0.931 (p = 0.687), respectively, per patient.Contrast-enhanced PET/MR is as accurate as contrast-enhanced PET/CT in determining the potential resectability of head and neck cancer. Although no significant difference was found, there was a tendency towards more reliable results obtained with PET/MR.