Rationale: The aims of this multicenter study were to identify clinical and preoperative PET/CT parameters predicting Overall Survival (OS) and Distant Metastasis Free Survival(DMFS) from a cohort of Head and Neck Squamous Cell Carcinoma (HNSCC) patients treated with surgery, to generate a prognostic model of OS and DMFS and to validate this prognostic model with an independent cohort. Materials and Methods: A total of 382 consecutive HNSCC patients divided into training (n = 318) and validation cohorts (n = 64) were retrospectively included. The following PET/CT parameters were analyzed: clinical parameters, SUVmax, SUVMean, Metabolic Tumor Volume (MTV), Total Lesion Glycolysis (TLG) and distance parameters for the primary tumor and lymph nodes defined by two segmentation methods (relative SUVmax threshold and absolute SUV threshold). Cox analyses were performed for OS and DMFS in the training cohort. The c-index was used to identify highly prognostic parameters. These prognostic parameters were externally tested in the validation cohort. Results: In multivariable analysis, the significant parameters for OS were T stage and Nodal-MTV, achieving a c-index of 0.64 (p<0.001). For DMFS, the significant parameters were T stage, Nodal-MTV and maximal tumor-node distance, with a c-index of 0.76 (p<0.001). These combinations of parameters were externally validated, achieving c-indices of 0.63 (p<0.001) and 0.71 (p<0.001) for OS and DMFS, respectively. Conclusion: The Nodal MTV associated with maximal distance between the primary tumor and the lymph node was significantly correlated with the risk of DMFS. Moreover, this parameter in addition to clinical parameters was associated with higher risk of death. These prognostic factors may be used to tailor individualized treatment.