Plasma D-dimer has been used as a complementary initial diagnostic marker for acute aortic dissection (AAD). However, its prognostic role in patients with Stanford type A AAD has not been clarified. We prospectively enrolled a consecutive series of patients with suspect AAD presented to our emergency department and measured the plasma D-dimer level (Stago-evolution, France) immediately following the admission. The diagnosis of type A AAD was confirmed by aorta angiography with multidetector computed tomography for each patient. Patients were divided into two groups: the deceased group, who died during hospitalization, and the survival group. The predictive value of D-dimer for in-hospital mortality was determined by using univariate and multivariate Cox proportional hazards analyses. A total of 133 patients with Stanford type A AAD were included. During hospitalization, death occurred in 19 (14.3%) patients. The average hospitalization period was 12.2 days. The plasma D-dimer level of the deceased group was significantly higher than that of the survival group (14.7 ± 8.1 vs. 9.0 ± 7.2 μg/ml, P = 0.003). The in-hospital mortality was significantly higher in patients with plasma D-dimer level of at least 20 μg/ml than in those with plasma D-dimer level less than 20 μg/ml (32.3 vs. 7.5%, log rank P < 0.001). In patients not receiving surgical treatment, the in-hospital mortality was significantly higher in patients with plasma D-dimer of at least 20 μg/ml than that in those with plasma D-dimer less than 20 μg/ml (52.4 vs. 16.7%, P = 0.007). After adjustment for age, systolic blood pressure, platelet counts, and intervals from symptom onset to hospital, a high admission D-dimer level (≥20 μg/ml) was still a powerful independent predictor of in-hospital mortality (hazard ratio 3.195, 95% confidence interval 1.110-9.196, P = 0.031). However, the predictive value of high admission D-dimer level disappeared when surgery was added to the Cox multivariate model. Our results suggest a high admission D-dimer level (≥20 μg/ml) might be a powerful predictor for increased in-hospital mortality in patients with Stanford type A AAD, and these patients may benefit more from surgical intervention.