PurposeTo assess the likelihood of occult infection in patients with clinically unsuspected orthopedic implants duringStaphylococcus aureusbacteremia (SAB).MethodsIn a retrospective study in two Dutch hospitals, we included all patients with SAB between 2013 and 2020 with one or more orthopedic implants in whom [18F]FDG-PET/CT was performed. The primary outcome was the percentage of patients who had an orthopedic implant-related infection byS. aureus. We also compared clinical parameters in patients with clinically suspected and unsuspected implants.ResultsFifty-five of 191 (29%) orthopedic implants in 118 SAB patients included had clinical signs of infection. Of all 136 unsuspected implants, 5 (3%, all arthroplasties), showed increased [18F]FDG uptake around the prosthesis on [18F]FDG-PET/CT. The clinical course of these patients without clinically overt infection or relapse of bacteremia during follow-up of a median of 48 months (range 0–48), however, argued against prosthetic joint infection.ConclusionAlthough orthopedic implants are evidently a risk factor for metastatic infection during SAB, the absence of clinical symptoms obviate the need of additional investigations or prolonged antibiotic treatment.