Objective The purpose of this study was to assess the clinical importance of 18F-FDG-PET/CT used in the extra cardiac work-up of patients with infective endocarditis (IE). Background IE is a serious condition with a significant mortality. Besides the degree of valvular involvement, the prognosis relies crucially on the presence of systemic infectious embolism. Methods Seventy-two patients (71% males and mean age 63 ± 17 years) with IE were evaluated with 18F-FDG-PET/CT in addition to standard work-up including patient history, physical examination, conventional imaging modalities, and weekly interdisciplinary conferences. When previous unknown lesions detected by 18F-FDG-PET/CT were confirmed by succeeding examinations, they were considered true positive new findings and were further assessed for their clinical importance . Number needed to investigate was calculated as the number of patients who needed to undergo 18F-FDG-PET/CT to find at least one clinical important true positive new finding , not identified by standard work-up prior to 18F-FDG-PET/CT. Results 18F-FDG-PET/CT detected 114 lesions and 64 were true positive , of which 25 were new findings and detected in 17 patients. In 11 patients, the lesions were considered to have a clinical importance; osteomyelitis ( n = 7), iliopsoas abscess ( n = 1), gastrointestinal lesions ( n = 2), and vascular prosthetic graft ( n = 1). Number needed to investigate was 7 (11 of 72 patients). Conclusions 18F-FDG-PET/CT detected lesions of clinical importance in one of seven IE patients and may be a substantial imaging technique for tracing peripheral infectious embolism due to IE. Thus, 18F-FDG-PET/CT may help to guide adequate therapy and thereby improve the prognosis of patients with IE.