Objective: A substantial number of patients with acute aortic syndrome (AAS) require invasive therapy because of disease progression. Our study aimed to assess the impact of positron emission tomography (PET)/computed tomography (CT) and serological markers of inflammation to identify patients at high risk for disease progression. Methods: 33 patients with AAS (thoracic aortic aneurysm 5, thoracic aortic dissection 14, penetrating aortic ulcer 8, intramural haematoma 6) were included. After intravenous administration of [18F] fluorodeoxyglucose a non-contrast enhanced PET/CT of the body trunk and CT angiography of the entire aorta was performed. Serological levels of D-dimers and C-reactive protein (CRP) were measured in all patients. Follow-up imaging was performed to detect disease progression. Results: 11 (33%) of 33 patients showed elevated tracer uptake within the aortic pathology, whereas 22 patients were PET-negative. In 23 patients a CRP level exceeding 1.0 mg/dl or a D-dimer level larger than 250 μg/l was found. The follow-up time was 224 (195) days. Nine of 11 PET-positive patients (82%) showed progression of AAS. In contrast, 55% of PET-negative patients showed stable disease or regression during the follow-up period. Kaplan-Meier analysis showed a clear, but not yet significant trend to longer survival in PET-negative patients, whereas elevated CRP and D-dimers did not allow for distinguishing of high-risk patients. Conclusions: Vessel wall inflammation was found in one-third of the patients with AAS and this patient group seems to have a high risk for disease progression. These initial results needs further investigation.