Background: The research of the sensitivity and specificity point-of-care testing (POCT) of D-dimer as a diagnostic protocol for differential diagnosis of Stanford Type A aortic syndrome (hereafter as TAAS) mimicking ST-elevated myocardial infarction (STEMI) with regular STEMI in the emergency department is limited. Methods: Full medical information of 32 patients confirmed TAAS and 527 patients confirmed STEMI from January 1st, 2016 to October 1st, 2021 were retrospectively analyzed in Shanghai Tenth People's Hospital of Tongji University. Results: The baseline characteristics of two groups of patients were well-balanced post propensity score matching (PSM) analysis, and each group had 32 patients enrolled. Patients in the STEMI group had higher positive cardiac troponin I (cTNI) (0.174 ng/ml vs. 0.055 ng/ml, P = 0.008) results but lower D-dimer (0.365μg/ml vs. 31.50μg/ml, P < 0.001) results than the TAAS group. The D-dimer cutoff value of 2.155μg/ml had the best sensitivity of 100% and specificity of 96.9%, and the positive predictive value (PPV) as well as the negative predictive value (NPV) of the cutoff value were 96.9 and 100%, respectively, in total 64 patients, the area under the curve (AUC) values were 0.998 (95% CI:0.992-1.000, P < 0.001) for the D-dimer. No significant correlation between the D-dimer concentration and the time from symptoms onset to first medical contact in both groups (TAAS group: r = − 0.248, P = 0.170; STEMI group: r = − 0.159, P = 0.383) or significant correlation between D-dimer and creatine clearance (TAAS group: r = − 0.065, P = 0.765; STEMI group: r = 0.222, P = 0.221). The total in-hospital mortality for the patients with TAAS presenting as STEMI was 62.5% (20/32). The mortality rate for TAAS patients confirmed by computed tomography angiography (CTA) was significantly lower (40% vs. 82.4%, P = 0.014) than the mortality rate for TAAS patients confirmed by coronary angiography (CAG) and had a longer average survival time (log-rank = 0.015), less peri-surgical complications especially gastrointestinal hemorrhage (0.00% vs. 55.6%, P < 0.001). CTA diagnosis can reduce the mortality rate by 67.5% (95%CI:0.124-0.850, P = 0.16). Conclusions: The POCT D-dimer with cut-off 2.155μg/ml would be useful to rule-out TAAS mimicking STEMI from regular STEMI prior to reperfusion therapy. CTA diagnosis is effective in reducing the probability of perioperative complications and lowering perioperative mortality than CAG diagnosis in TAAS patients. [ABSTRACT FROM AUTHOR]