Aim To explore the differential risk assessment of acute aortic syndrome (AAS) and non-ST-segment elevation myocardial infarction (NSTEMI) in patients with chest pain less than 3 hours. Methods 69 patients with AAS and 136 patients with NSTEMI were retrospectively analyzed. The data of the two groups were statistically analyzed and the differences between the two groups were compared. Univariate and multivariate Logistic regression analysis were used to evaluate the differential risk factors of AAS and NSTEMI. The area under curve (AUC) of receiver operating characteristic (ROC) of differential risk factors was compared. The value of each factor in distinguishing AAS and NSTEMI was analyzed, and the best cut-off value of partial difference risk factors was determined. Results Multivariate Logistic regression analysis showed that D-dimer (OR 8.2,5% CI 4.064～19.366), platelet distribution width (PDW) (OR 1.5,5% CI 1.253～2.133), unconjugated bilirubin (UCB) (OR 1.9,5% CI 1.003～1.317), systolic blood pressure (SBP) (OR 1.5,5% CI 1.006～1.045) were higher risk factors of AAS compared with NSTEMI. ROC curve analysis showed that AUCD-dimer＝0.944 (95%CI 0.897～0.973) and AUCPDW＝0.794 (95%CI 0.724～0.853). The optimal cut-off value of D-dimer and PDW in identifying AAS from NSTEMI was determined by using the Youden index of ROC curve. The cut-off point of ROC curve of D-dimer was 247.5 μg/L, the sensitivity was 95.7%, and the specificity was 83.8%; The cut-off point of ROC curve of PDW was 16.05%, the sensitivity was 58.8%, and the specificity was 95.6%. Conclusions D-dimer, PDW, UCB and SBP are the differential risk factors of AAS and NSTEMI. When D-dimer is lower than 247.5 μg/L, AAS can be effectively excluded, and when PDW is higher than 16.05%, AAS will probably occur.