We report our experience with using integrated molecular and anatomic hybrid imaging to assess infection in patients who have a left-ventricular-assist device (LVAD). Thirteen (99m)Tc-exametazime-leukocyte planar and SPECT/CT scans were obtained for 8 consecutive patients who had an implanted LVAD. SPECT/CT was used to assess suspected device-related infections (n = 8) and to evaluate the efficiency of current antibiotic therapy (n = 5). Device-related infection was seen on 8 of the 13 scans. SPECT/CT was positive for infection in all 8 patients, whereas planar scans were positive in 6 of 8. SPECT/CT provided relevant information on the extent of infection and its exact location in all patients. Additional distant infectious foci were demonstrated in 3 of 13 patients. SPECT/CT led to an accurate diagnosis of LVAD-related infection, revealing both anatomic location and extent. This noninvasive approach could lead to improved therapeutic strategies.