Purpose 18 F-FDG PET/CT (PET/CT) is a useful tool for the diagnosis of aortic graft infection (AGI), but has rarely been used to influence therapeutic decisions during follow-up. We aimed to study the role of PET/CT in the long-term monitoring of patients. Methods Participants of the prospective Vascular Graft Infection Cohort Study (VASGRA) were included if they had microbiologically proven AGI. We quantified the metabolic activity in PET/CT by using maximum standardized uptake value (SUV max ) and further classified it as being focal or diffuse. Multivariable linear regression models were fit using generalized estimating equations to investigate factors associated with SUV max over time. Results Sixty-eight participants with AGI contributed to 266 PET/CTs including 36 examinations performed after stop of antimicrobial therapy. Higher C-reactive protein (CRP) (adjusted coefficient per log 10 mg/L 0.05 95% C.I. 0.02–0.08) was associated with higher SUV max . CRP, metabolic and clinical findings informed the decision to either start (medians of SUV max 7.1 and CRP 31.5 mg/L; 100% focal uptake), escalate (SUV max 9.5; CRP 31.5; 100% focal uptake), continue (SUV max 6.0; CRP 9.95 mg/L; 90% focal uptake), or stop (SUV max 4.3; CRP 3.5 mg/L; 61% focal uptake) antibiotic treatment. Of note, decisions to escalate or continue antibiotic treatment were taken despite normal CR P values in 12.5 and 35.7% of PET/CTs, respectively. Conclusions Consecutive PET/CTs could influence the clinical decision-making in patients with AGI in the near future. More studies on the use of PET/CT in case of aortic graft infection may offer the potential for individualized treatment approaches. CLINICALTRIALS.GOV IDENTIFIER NCT01821664.