BACKGROUND: To determine whether 18 F-PET/CT is able to identify treatment response as early as 1 week after the end of chemoradiotherapy, whether 18 F-PET/CT can identify prognostic markers concerning progression free survival and can identify patients who need additional consolidation therapy. METHODS: A total of 54 patients with head and neck cancer were prospectively enrolled in this single-center, randomized study from 03/2012-04/2015. Patients underwent FDG-PET/CT imaging at three predefined time points: pretreatment (PET/CT1), 1 week postprimary radiochemotherapy (PET/CT2) and 3 months postprimary radiochemotherapy (PET/CT3). Tumors were assessed quantitatively based on size and glucose uptake (SUVmax) concerning response at each time point. Response assessment was correlated with progression free survival. All patients had a minimum follow-up period of 18 months. Multivariate regression analysis was performed to find independent predictors for progression free survival (PFS). RESULTS: Thirty-two (32) patients (64%) overall remained disease free, 11 patients (22%) had recurrence and 7 patients (14%) had persistent disease. There was no significantly different metabolic parameter ratio found concerning responders and nonresponders at posttreatment (PET/CT2 and 3) time points (P > .05) during clinical follow-up. Multivariate regression analysis demonstrated both SUVmax and diameter assessed at time point PET/CT3 represent independent predictors of progression free survival (PFS). There was also no statistically significant difference in PFS between responders and nonresponders by means of PET/CT2 in both study arms (P > .05). Imaging responders at time point PET/CT3 showed a significantly longer PFS compared to nonresponders after the end of consolidation therapy (P < .01). CONCLUSIONS: Early response of head/neck cancer after radiochemotherapy can be accurately assessed with PET/CT 1 week after RCT. SUVmax and lesion diameter are independent predictors of PFS at time point PET/CT3. PET/CT2 has no prognostic value concerning PFS and cannot identify high risk patients for consolidation therapy. Imaging responders showed a significantly longer PFS compared to nonresponders and therefore PET/CT might serve as a prognostic biomarker. TRIAL REGISTRATION: Clinical Trials.gov identifier: NCT01435252.