The aim of the study was to evaluate the ability to detect extra-cardiac foci by means of whole-body 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in patients with definite endocarditis (IE) according to the modified Duke criteria and investigate the clinical impact of the findings. From January 2011 to December 2015 we included 178 patients (mean age 66 ± 14 years, 25% female) with IE in this multicentre study. FDG-PET/CT was part of the work-up for extra-cardiac foci in the including hospitals and was performed at a median of 9 days (IQR 10) after IE was diagnosed. In 114 patients FDG-PET/CT identified 166 lesions: 52 (31%) infectious lesions, 21 (13%) cases of cancer, 7 (4%) cases of embolism, 60 (36%) reactive findings, and 26 (16%) other types of lesions. A total of 74 new extra-cardiac findings, not previously discovered by other modalities, were identified in 62 patients and resulted in additional investigations in 29 patients and a change in treatment in 18 patients (10%). The most frequent diagnoses discovered by FDG-PET/CT were colon polyps, cancer, and spondylodiscitis. There was a higher rate of findings leading to a change in treatment in patients above 67 years of age infected with other bacterial aetiologies than streptococci. FDG-PET/CT was useful to detect extra-cardiac foci. FDG-PET/CT findings may lead to unnecessary investigations. One out of 10 the patients with definite endocarditis had underwent a change in treatment regimen based on the FDG-PET/CT findings.