OBJECTIVE: The objective of this study was to investigate the independent prognostic value of dual-time-point F-fluorodeoxyglucose (F-FDG) PET-CT imaging in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Patients referred to our department to undergo F-FDG PET-CT for staging of HNSCC were prospectively included. Each patient was scanned using a Philips Gemini PET-CT system 1 h (early acquisition) and 2 h (delayed acquisition) after injection. An intratumoral retention index (RI) of F-FDG was measured for each examination by the dual-time-point method. Event-free survival (EFS) and overall survival (OS) were determined by the Kaplan-Meier method and compared with the conventional maximum standardized uptake value (SUVmax) at 60 min, SUVmax at 120 min, and RI in univariate and multivariate analyses including the usual prognostic factors such as age, sex, primary site, SCC histologic grade, and American Joint Committee on Cancer stage (I, II, III, and IV). RESULTS: Sixty-six consecutive patients (60 men and six women; mean age=61±9 years) were included in the study. In univariate analysis, besides age and stage, RI was predictive of EFS (P=0.01) but not of OS (P=0.1), whereas SUVmax at 60 min was not predictive of EFS (P=0.18) or OS (P=0.08) and SUVmax at 120 min was predictive of OS (P=0.02) but not of EFS (P=0.05). In multivariate analysis, RI persisted as an independent predictive factor for EFS (P=0.02) but not SUVmax at 120 min for OS (P=0.12). CONCLUSION: Our results suggest an additional prognostic interest of RI measured by dual-time-point F-FDG PET-CT, independent of usual prognostic factors, in patients with HNSCC.