Background— The immune system orchestrates the repair of infarcted myocardium. Imaging of the cellular inflammatory response by 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/magnetic resonance imaging in the heart has been demonstrated in preclinical and clinical studies. However, the clinical relevance of post-MI 18 F-FDG uptake in the heart has not been elucidated. The objective of this study was to explore the value of 18 F-FDG positron emission tomography/magnetic resonance imaging in patients after acute myocardial infarction as a biosignal for left ventricular functional outcome. Methods and Results— We prospectively enrolled 49 patients with ST-segment–elevation myocardial infarction and performed 18 F-FDG positron emission tomography/magnetic resonance imaging 5 days after percutaneous coronary intervention and follow-up cardiac magnetic resonance imaging after 6 to 9 months. In a subset of patients, 99m Tc-sestamibi single-photon emission computed tomography was performed with tracer injection before revascularization. Cellular innate immune response was analyzed at multiple time points. Segmental comparison of 18 F-FDG-uptake and late gadolinium enhancement showed substantial overlap (κ=0.66), whereas quantitative analysis demonstrated that 18 F-FDG extent exceeded late gadolinium enhancement extent (33.2±16.2% left ventricular myocardium versus 20.4±10.6% left ventricular myocardium, P r =0.87, P high /CD16 + monocytes correlated with the infarction size and 18 F-FDG signal extent ( r =0.53, P r =0.42, P 18 F-FDG uptake in the infarcted myocardium was highest in areas with transmural scar, and the standardized uptake value mean was associated with left ventricular functional outcome independent of infarct size (Δ ejection fraction: P P P Conclusions— In this study, the intensity of 18 F-FDG uptake in the myocardium after acute myocardial infarction correlated inversely with functional outcome at 6 months. Thus, 18 F-FDG uptake in infarcted myocardium may represent a novel biosignal of myocardial injury.