Abstract Background Several studies have suggested that in patients with Staphylococcus aureus bacteremia (SAB) 18F fluorodeoxyglucose positron emission tomography/computed tomography (18FFDG-PET/CT) improves outcome. However, these studies often ignored possible immortal time bias. Methods Prospective multicenter cohort study in 2 university and 5 non-university hospitals, including all patients with SAB. 18FFDG-PET/CT was performed on clinical indication as part of usual care. Primary outcome was 90-day all-cause mortality. Effect of 18FFDG-PET/CT was modeled with a Cox proportional hazards model using 18FFDG-PET/CT as a time-varying variable and corrected for confounders for mortality (age, Charlson score, positive follow-up cultures, septic shock, and endocarditis). Secondary outcome was 90-day infection-related mortality (assessed by adjudication committee) using the same analysis. In a subgroup-analysis, we determined the effect of 18FFDG-PET/CT in patients with high risk of metastatic infection. Results Of 476 patients, 178 (37%) underwent 18FFDG-PET/CT. Day-90 all-cause mortality was 31% (147 patients), and infection-related mortality was 17% (83 patients). The confounder adjusted hazard ratio (aHR) for all-cause mortality was 0.50 (95% confidence interval CI: .34–.74) in patients that underwent 18FFDG-PET/CT. Adjustment for immortal time bias changed the aHR to 1.00 (95% CI .68–1.48). Likewise, after correction for immortal time bias, 18FFDG-PET/CT had no effect on infection-related mortality (cause specific aHR 1.30 95% CI .77–2.21), on all-cause mortality in patients with high-risk SAB (aHR 1.07 (95% CI .63–1.83) or on infection-related mortality in high-risk SAB (aHR for 1.24 95% CI .67–2.28). Conclusions After adjustment for immortal time bias 18FFDG-PET/CT was not associated with day-90 all-cause or infection-related mortality in patients with SAB. After correction for immortal time bias, 18F fluorodeoxyglucose positron emission tomography/computed tomography (18FFDG-PET/CT) does not influence all-cause or infection-related mortality in patients with Staphylococcus aureus bacteremia. Graphical abstract This graphical abstract is also available at Tidbit: https://tidbitapp.io/tidbits/positive-impact-of-18f-fdg-pet-ct-on-mortality-in-patients-with-staphylococcus-aureus-bacteremia-explained-by-immortal-time-bias-b4db7e26-22b3-4771-bad6-9eba9b0c3dcc/update