Metastatic infection is an important complication of Staphylococcus aureus bacteremia (SAB). Early diagnosis of metastatic infection is crucial, as specific treatment is required. However, metastatic infection can be asymptomatic and difficult to detect. In this study, we investigated the role of (18)F-FDG-PET/CT in patients with SAB for detection of metastatic infection and its consequences for treatment and outcome. Methods: All patients with SAB at Radboud university medical center were included between January 2013 and April 2016. Clinical data and results of (18)F-FDG-PET/CT and other imaging techniques, including echocardiography, were collected. Primary outcomes were newly diagnosed metastatic infection by (18)F-FDG-PET/CT, subsequent treatment modifications, and outcome. Results: A total of 184 patients were included and (18)F-FDG-PET/CT was performed in 105 patients of whom 99 had a high-risk bacteremia. (18)F-FDG-PET/CT detected metastatic infectious foci in 73.7% of these high-risk patients. In 71.2% of patients with metastatic infection, no signs and symptoms suggesting metastatic complications were present before (18)F-FDG-PET/CT was performed. (18)F-FDG-PET/CT led to a total of 104 treatment modifications in 74 patients. Three-month mortality was higher in high-risk bacteremia patients without (18)F-FDG-PET/CT performed compared to those in whom (18)F-FDG-PET/CT was performed (32.7% versus 12.4%, P = 0.003). In multivariate analysis, (18)F-FDG-PET/CT was the only factor independently associated with reduced mortality (P = 0.005; OR, 0.204; 95% CI, 0.066-0.624). A higher co-morbidity score was independently associated with increased mortality (P = 0.003; OR, 1.254; 95% CI, 1.078-1.457). Conclusion:(18)F-FDG-PET/CT is a valuable technique for early detection of metastatic infectious foci, often leading to treatment modification. Performing(18)F-FDG-PET/CT is associated with significantly reduced three-month mortality.