INTRODUCTION: The purpose of this study was to assess the predictive and prognostic role of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in candidates with stage III non-small-cell lung cancer (NSCLC) to neoadjuvant chemotherapy. PATIENTS AND METHODS: Sixty-six patients with stage III NSCLC treated with induction chemotherapy from March 2013 to December 2017 were retrospectively identified. Response assessment were evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and European Organisation for Research and Treatment of Cancer (EORTC) criteria. 18F-FDG PET/CT metabolic parameters were analyzed as absolute values as well as percentage changes (Δ) between 2 consecutive scans, for primary tumor (T) and for regional lymph nodes (N). All clinical variables and metabolic parameters were compared with treatment response and correlated with progression-free survival (PFS) and overall survival (OS), based on a median follow-up of 9.4 months. RESULTS: Post-induction therapy standardized uptake value (SUV)max_T, SUVmean_T, metabolic tumor volume (MTV_T), and total lesion glycolysis of the tumor (TLG_T) varied significantly between responders and non-responders (6.6 vs. 13.8; P = .001; 4.2 vs. 8.1; P < .001; 6 vs. 17.9; P = .002; and 24.1 vs. 136.3; P < .001, respectively). Likewise, percentage changes (Δ_T) were significantly different between the 2 groups (P < .001). Along with primary tumor, also post-SUVmax_N, post-SUVmean_N, and post-TLG_N (P = .024, P = .015, and P = .024, respectively), as well as all percentage changes (Δ_N) were different between responders and non-responders. RECIST 1.1 and EORTC response classifications were discordant in 27 patients (40.9%; κ = 0.265; P = .003). On multivariate analysis, post-TLG_N was an independent predictor for both PFS and OS, whereas RECIST 1.1 was a predictor only for OS. CONCLUSIONS: Several metabolic parameters may differentiate responders from non-responders following neoadjuvant chemotherapy in stage III NSCLC. As compared with RECIST 1.1, EORTC seems to be more appropriate for evaluation therapeutic response. Finally, post-TLG_N has significant prognostic information.