OBJECTIVE: To investigate the role of plasma D-dimer in differentiating fatal chest pain due either to acute myocardial infarction (AMI), acute pulmonary embolism (APE) or acute aortic dissection (AAD) in emergency department. METHODS: The data of a total of 445 consecutive patients complaining chest (back) pain and/or dyspnea who visited emergency department of Peking University Third Hospital from January 2011 to January 2012 were retrospectively analyzed. All cases were either diagnosed as AMI, APE or AAD finally. D-dimer concentrations were assessed and compared among different groups. The receiver operating characteristic curve (ROC curve) was established. The potency of D-dimer in distinguishing AMI, non-ST-segment elevation myocardial infarction (NSTEMI) by difference in values was assessed. RESULTS: Finally, 438 cases were enrolled, including 327 AMI [253 ST-segment elevation myocardial infarction (STEMI) and 74 NSTEMI], 76 APE and 35 AAD cases. The D-dimer concentrations in AMI group [0.21(0.15, 0.33) mg/L] were significantly lower than those in APE group [1.06 (0.86, 3.01) mg/L, Z=-11.416, P<0.001], AAD group [1.79 (0.83, 3.37) mg/L, Z=-8.715, P<0.001], APE/AAD group [1.15 (0.85, 3.13) mg/L, Z=-13.509, P<0.001]. The D-dimer concentrations in STEMI group were significantly lower than those in NSTEMI group [mg/L: 0.20 (0.15, 0.30) vs. 0.24 (0.17, 0.54), Z=-3.248, P=0.001]. The area under ROC curve (AUC) to discriminate AMI from APE/AAD was 0.929±0.015, and optimal value was 0.535 mg/L. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), negative likelihood ratio (NLR) with cut-off value of 0.535 mg/L were 86.2%, 93.7%, 97.6%, 69.8%,13.68, 0.15, while sensitivity, specificity, PPV, NPV, PLR, NLR with cut-off value of 0.5 mg/L were 84.4%, 93.7%, 97.5%, 67.1%, 13.40, 0.17. The AUC to discriminate NSTEMI from APE/AAD was 0.881±0.028. Sensitivity, specificity, PPV, NPV with cut-off value of 0.535 mg/L were 75.7%, 93.7%, 88.9%, 85.2%, while sensitivity, specificity, PPV, NPV with cut-off value of 0.5 mg/L were 70.3%, 93.7%, 88.1%, 82.5%, respectively. CONCLUSIONS: D-dimer is a better index in differentiating AMI from APE/AAD in emergency setting, guiding further examination and therapy, and increasing diagnosis efficiency.