Radiation-induced changes may cause a non-malignant high 2-deoxy-2-[F]fluoro-d-glucose (FDG)-uptake. The 3'-deoxy-3'-[F]fluorothymidine (FLT)-PET/CT performs better in the differential diagnosis of inflammatory changes and lung lesions with a higher specificity than FDG-PET/CT. We investigated the association between post-radiotherapy FDG-PET-parameters, FLT-PET-parameters, and outcome. Sixty-one patients suspected for having a relapse after definitive radiotherapy for lung cancer were included. All the patients had FDG-PET/CT and FLT-PET/CT. FDG-PET- and FLT-PET-parameters were collected from within the irradiated high-dose volume (HDV) and from recurrent pulmonary lesions. For associations between PET-parameters and relapse status, respectively, the overall survival was analyzed. Thirty patients had a relapse, of these, 16 patients had a relapse within the HDV. FDG-SUV and FLT-SUV were higher in relapsed HDVs compared with non-relapsed HDVs (median FDG-SUV: 12.8 vs. 4.2; < 0.001; median FLT-SUV 3.9 vs. 2.2; < 0.001). A relapse within HDV had higher FDG-SUV (median FDG-SUV: 7.1 vs. 3.5; = 0.014) and was larger (median metabolic tumor volume (MTV): 2.5 vs. 0.7; 0.014) than the relapsed lesions outside of HDV. The proliferative tumor volume (PTV) was prognostic for the overall survival (hazard ratio: 1.07 pr cm [1.01-1.13]; = 0.014) in the univariate analysis, but not in the multivariate analysis. FDG-SUV and FLT-SUV may be helpful tools for differentiating the relapse from radiation-induced changes, however, they should not be used definitively for relapse detection.