The objective of this retrospective study was to determine the role of 18F-FDG PET/CT in a large cohort of 495 patients with metastatic neuroendocrine neoplasms (NENs) who were treated with peptide receptor radionuclide therapy (PRRT) with a long-term follow-up. The 495 patients were treated with 177Lu- or 90Y-DOTATOC/DOTATATE PRRT between Feb. 2002 and July 2018. All subjects received both 68Ga-DOTATOC/TATE/NOC and 18F-FDG PET/CT before treatment and were followed 3-189 mo. Kaplan-Meier anal., log-rank testing (Mantel-Cox), and Cox regression anal. were performed for overall survival (OS) and progression-free survival (PFS). One hundred ninety-nine patients (40.2%) presented with pancreatic NENs, 49 with cancer of unknown primary, and 139 with midgut NENs, whereas the primary tumor was present in the rectum in 20, in the lung in 38, in the stomach in 8, and in other locations in 42. 18F-FDG PET/CT was pos. in 382 (77.2%) patients and neg. in 113 (22.8%) before PRRT, whereas 100% were 68Ga-DOTATOC/TATE/NOC-pos. For all patients, the median PFS and OS, defined from the start of PRRT, were 19.6 mo and 58.7 mo, resp. Pos. 18F-FDG results predicted shorter PFS (18.5 mo vs. 24.1 mo; P = 0.0015) and OS (53.2 mo vs. 83.1 mo; P < 0.001) than neg. 18F-FDG results. Among the cases of pancreatic NENs, the median OS was 52.8 mo in 18F-FDG-pos. subjects and 114.3 mo in 18F-FDG-neg. subjects (P = 0.0006). For all patients pos. for 18F-FDG uptake, and a ratio of more than 2 for the highest SUVmax on 68Ga-somatostatin receptor (SSTR) PET to the most 18F-FDG-avid tumor lesions, the median OS was 53.0 mo, compared with 43.4 mo in those patients with a ratio of less than 2 (P = 0.030). For patients with no 18F-FDG uptake (complete mismatch imaging pattern), the median OS was 108.3 mo vs. 76.9 mo for an SUVmax of more than 15.0 and an SUVmax of 15.0 or less on 68Ga-SSTR PET/CT, resp. The presence of pos. lesions on 18F-FDG PET is an independent prognostic factor in patients with NENs treated with PRRT. Metabolic imaging with 18F-FDG PET/CT complements the mol. imaging aspect of 68Ga-SSTR PET/CT for the prognosis of survival after PRRT. High SSTR expression combined with neg. 18F-FDG PET/CT results is associated with the most favorable long-term prognosis.