The purpose of this research was to assess the value of systemic inflammatory biomarkers in the detection of acute aortic dissection (AD). Rapid diagnosis and initiation of treatment is pivotal for patients with acute AD. So far, there is no laboratory test to aid the diagnosis. Plasma fibrin D-dimers, white blood cell (WBC) count, C-reactive protein (CRP), and fibrinogen were determined in 64 chest-pain (CP) patients (acute AD, n = 16; pulmonary embolism [PE], n = 16; acute myocardial infarction [AMI], n = 16; non-cardiac CP, n = 16); 32 asymptomatic patients with chronic AD served as a control group. All acute AD patients showed highly elevated D-dimer values that were similar to PE patients (2,238 1,765 μg/l vs. 1,531 837 μg/l, p = 0.15) but significantly higher than in chronic AD, AMI, or CP patients (p < 0.001). The WBC count was significantly increased in patients with acute AD compared with the other groups (p < 0.001); in addition, CRP values differed only non-significantly from PE patients(p = 0.71). There were no differences in the fibrinogen levels between the groups. D-dimers are highly elevated in both acute PE and acute AD. Patients with acute AD show significant systemic inflammatory reactions. Measurement of D-dimers may be a valuable addition to the current diagnostic work-up of patients with suspected AD.