Abstract Objectives The purpose of this study was to explore the diagnostic usefulness of hybrid cardiac magnetic resonance (CMR) and positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) for active cardiac sarcoidosis. Background Active cardiac sarcoidosis (aCS) is underdiagnosed and has a high mortality. Methods Patients with clinical suspicion of aCS underwent hybrid CMR/PET with late gadolinium enhancement (LGE) and FDG to assess the pattern of injury and disease activity, respectively. Patients were categorized visually as magnetic resonance (MR)+PET+ (characteristic LGE aligning exactly with increased FDG uptake), MR+PET− (characteristic LGE but no increased FDG), MR−PET− (neither characteristic LGE nor increased FDG), and MR−PET+ (increased FDG uptake in absence of characteristic LGE) and further characterized as aCS+ (MR+PET+) or aCS− (MR+PET−, MR−PET−, MR−PET+). FDG uptake was quantified using maximum target-to-normal-myocardium ratio and the net uptake rate ( K i ) from dynamic Patlak analysis. Receiver operating characteristic methods were used to identify imaging biomarkers for aCS. FDG PET was assessed using computed tomography/PET in 19 control subjects with healthy myocardium. Results A total of 25 patients (12 males; 54.9 ± 9.8 years of age) were recruited prospectively; 8 were MR+PET+, suggestive of aCS; 1 was MR+PET−, consistent with inactive cardiac sarcoidosis; and 8 were MR−PET−, with no imaging evidence of cardiac sarcoidosis. Eight patients were MR−PET+ (6 with global myocardial FDG uptake, 2 with focal-on-diffuse uptake); they demonstrated distinct K i values and hyperintense maximum standardized uptake value compared with MR+PET+ patients. Similar hyperintense patterns of global (n = 9) and focal-on-diffuse (n = 2) FDG uptake were also observed in control patients, suggesting physiological myocardial uptake. Maximum target-to-normal-myocardium ratio values were higher in the aCS+ group (p < 0.001), demonstrating an area under the curve of 0.98 on receiver operating characteristic analysis for the detection of aCS, with an optimal maximum target-to-normal myocardium ratio threshold of 1.2 (Youden index: 0.94). Conclusions CMR/PET imaging holds major promise for the diagnosis of aCS, providing incremental information about both the pattern of injury and disease activity in a single scan. (In Vivo Molecular Imaging MRI of Atherothrombotic Lesions; NCT01418313 )