BACKGROUND: (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) is recommended for diagnosis and evaluation of therapy in patients with cardiac sarcoidosis (CS). OBJECTIVES: FDG uptake parameters were investigated semi-quantitatively in biopsy-proven CS at time of diagnosis (CSD) and during immunosuppressive therapy (CST) and in controls. METHODS: We studied 11 patients with endomyocardial biopsy-proven CS and 15 controls. FDG uptake was assessed as myocardial-to-background ratio (MBR) of standardized uptake values in the 17-segment model and right ventricle in relation to clinical baseline parameters and changes during follow-up (FU). RESULTS: MBRs per cardiac segment in controls were below 2.1 in all control patients. In CSD, median MBR was 2.4 (IQR 1.3; 4.0), highest septal and anterobasal. In CST, median MBR was 1.5 (IQR 1.1; 1.7) with a significant reduction of mean MBRs from baseline per cardiac segment (z −9.5, p < 0.001). Patients with clinical progress showed higher MBRs and more affected cardiac segments before therapy (n = 2, MBR 4.3 ± 3.0, 18.0 ± 0) than patients with stable disease (n = 5, MBR 2.8 ± 1.2, 14.4 ± 4.6) or clinical improvement (n = 4, MBR 2.6 ± 2.5, 8.0 ± 7.4, p = n.s.) Applying a new score based on mean MBR times number of involved segments showed highest values in patients with clinical progression. CONCLUSION: MBRs per cardiac segment can be used as a semiquantitative tool to evaluate FDG uptake in patients with CS with a cut-off ≥2.1 for relevant pathologic uptake. The clinical course may correlate with the number of affected cardiac segments and the MBRs per segment.