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The usage of left-ventricular-assist device (LVAD) is increasing in patients presenting with advanced heart failure. However, device-related infections are a challenge to recognize and to treat, with an important morbidity and mortality rate. The role of nuclear medicine imaging remains not well established for LVAD infections. The present study compared the accuracy of positron emission tomography/computed tomography with 18F-fludeoxyglucose (18F-FDG PET/CT) and radiolabeled leucocyte scintigraphy for the diagnosis of infections in patients supported with a continuous-flow LVAD. From a prospectively maintained database, we retrospectively analyzed the diagnostic performance of radiolabeled leucocyte scintigraphy and 18F-FDG PET/CT in 24 patients who had a LVAD with a suspected device-related infection. Both examinations were routinely performed in all patients. Infection was assessed by the International Society for Heart and Lung Transplantation criteria. Twenty-four patients were included: 15 had a specific VAD infection (5 cardiac-LVAD and 10 driveline), 6 had a VAD-related infection, while 3 patients had a non-VAD-related infection. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 95.2%, 66.7%, 95.2%, 66.7%, and 91.6%, respectively, for 18F-FDG-PET; and 71.4%, 100%, 100%, 33.3%, and 75%, respectively, for leucocyte scintigraphy. 18F-FDG PET/CT showed significantly higher sensitivity (P = 0.01) than leucocyte scintigraphy. 18F-FDG PET/CT and radiolabeled leucocyte scintigraphy single-photon emission computed tomography carry high performance in the diagnostic of LVAD infections. 18F-FDG PET/CT shows significantly higher sensitivity and could be proposed as first-line nuclear medicine procedure.