O-(2-[F]fluoroethyl)-L-tyrosine positron-emission tomography/computed tomography (F-FET PET/CT) is well known in brain tumor management. Our study aimed to identify the prognostic value of F-FET PET/CT in high-grade gliomas (HGG) according the current 2016 World Health Organization (WHO) classification.Patients with histologically proven WHO 2016 HGG were prospectively included. A dynamic F-FET PET/CT was performed allowing to obtain 2 static PET frames (static frame 1: 20-40 minutes and static frame 2: 2-22 minutes). We analyzed static parameters (standard uptake value [SUV]max, SUVmean, SUVpeak, TBRmax, TBRmean, tumoral lesion glycolysis, and metabolic tumoral volume) for various isocontours (from 10% to 90%). PET parameters, clinical features, and molecular biomarkers were compared with progression-free survival (PFS) and overall survival (OS) in univariate and multivariate analysis.Twenty-nine patients were included (grade III n = 3, grade IV n = 26). Mean PFS and OS were, respectively, 8.8 and 13.9 months. According to univariate analysis, SUVmean, SUVpeak, TBRmax, and TBRmean were significantly correlated with OS. In static 1 analysis, TBRmax seemed to be the best OS prognostic parameter (P = .004). In static 2 analysis, TBRmean was the best parameter (P = .01). In static 1 analysis, only SUVpeak was significant (P = .05) for PFS. Good performance status (PS < 2; P < .0001) and extent of resection (P = .019) identified the subgroup of patients with the best OS. Only TBRmax (P = .026) and extent of resection (P = .025) remained significant parameters in multivariate analysis.Our data suggested that high TBRmax seemed to be the most significant OS independent prognostic factor in patients with newly diagnosed HGG.