Aim of this study was to investigate the relationship between ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) findings and serological biomarkers of inflammation and the related discriminant value of unfavourable outcome during follow-up in patients with acute aortic syndromes (AAS). Sixty patients with AAS underwent PET-CT imaging during the hospitalization along with measurement of C-reactive protein (CRP) and D-dimer (D-d) serum levels. An aortic wall pathology was considered PET-positive by a maximum standardized uptake value (SUV_max) >2.5. A combined endpoint of major adverse events (MAE) including aorta-related mortality, disease progression and re-intervention was used to compare patient subgroups at 3-year follow-up. PET-CT detected an elevated FDG uptake within the aortic wall in 25 (41.7 %) patients. PET-positive patients showed significantly increased CRP levels (10.0 ± 6.6 mg/dL) and tended to higher D-d levels (5.1 ± 3.9 mg/L), compared to PET-negative patients (5.8 ± 6.1 mg/dL and 3.1 ± 4.7 mg/L respectively; P = 0.048, P = 0.19). At 3-year follow-up, all-cause mortality and MAE were higher in the PET-positive (21.7 and 47.8 % respectively) than PET-negative group (0.0 and 13.3 % respectively; P = 0.012, P = 0.006). On Kaplan–Meier analysis, PET-positive patients were at higher risk of MAE (P = 0.031). This tendency was more evident by combining PET results with D-d levels at a cutoff value of 4.8 mg/L (P < 0.001). In patients with AAS, a pathological glucose uptake in aortic wall lesions by PET-CT was associated with high CRP levels and increased mortality and MAE at 3-year follow-up. The combination of PET results with D-d levels had the best discriminant value of MAE.