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Our purpose was to assess the diagnostic potential of simultaneously acquired ¹⁸F-FDG PET and MRI data sets for therapy response assessment of isolated limb perfusion (ILP) in patients with soft-tissue sarcomas (STS). In total, 45 patients with histopathologically verified STS were prospectively enrolled for an integrated ¹⁸F-FDG PET/MRI examination before and after ILP. Therapy response was assessed based on different MRI- and PET-derived morphologic (RECIST and the MR-adapted Choi criteria) and metabolic (PERCIST) criteria. In addition, a regression model was used combining relative changes in quantitative variables to predict treatment response under ILP. Histopathologic results after subsequent tumor resection served as the reference standard, and patients were categorized as responders or nonresponders on the basis of the 6-stage regression scale by Salzer-Kuntschik.