Objective: To determine the value of N-terminal pro-brain natriuretic peptide (NT-proBNP) and aortic diameter in predicting in-hospital mortality in acute aortic dissection (AD). Methods: A single-center prospective study was designed in the setting of University hospital in China. 122 patients with acute AD were enrolled. Admission plasma NT-proBNP levels and aortic diameter were measured. Results: Plasma NT-proBNP concentrations (P < 0.001), aortic diameter (P = 0.002), and admission systolic blood pressure (SBP) (P = 0.011) were significantly increased in patients who died compared to those who survived during hospitalization. Furthermore, aortic diameter had positive correlations with NT-proBNP levels (r = 0.270, P = 0.003) and admission diastolic blood pressure (DBP) (r = 0.202, P = 0.025), respectively. Multiple logistic regression analysis demonstrated that NT-proBNP >= 569.75 pg/ml and aortic diameter >= 40 mm were strongly associated with in-hospital mortality. The odds ratio (OR) and 95% confidence interval (CI) were 3.246, 1.212-8.693 (P = 0.019); and 2.917, 1.102-7.722 (P = 0.031), respectively. Moreover, when NT-proBNP >= 1325.6 pg/ml, the sensitivity and specificity of NT-proBNP in predicting in-hospital mortality risk were 55.2% and 95.7% (95% CI, 0.707-0.891; P < 0.001), respectively. In addition, when aortic diameter >= 47 mm, the sensitivity and specificity were 58.6% and 88.2% (95% CI, 0.607-0.841; P < 0.001), respectively. Conclusions: NT-proBNP >= 569.75 pg/ml and aortic diameter >= 40 mm were important risk factors and independently associated with acute AD in-hospital mortality. NT-proBNP >= 1325.6 pg/ml or aortic diameter >= 47 mm showed higher specificity in predicting in-hospital mortality. Using NT-proBNP and aortic diameter together showed better performance in predicting in-hospital mortality with higher sensitivity.