Acute aortic dissection (AAD) is often missed on initial assessment.The aim of our study was to identify features associated with misdiagnosis of AAD.We examined a total of 109 emergency room (ER) patients who were ultimately diagnosed with AAD. Misdiagnosis of AAD was defined as failure to diagnose AAD at the end of the initial assessment in the ER, and occurred in 17 patients (16%). The alternate diagnosis consisted of acute coronary syndrome (n=10), other cardiovascular disease (n=3), abdominal disease (n=3), and cerebral infarction (n=1). In the misdiagnosed patients, walk-in mode of admission to the ER (29% vs. 10%, p=0.042) and anterior chest pain (71% vs. 41%, p=0.025) were more frequent, and widened mediastinum (25% vs. 55%, p=0.023) was less frequent than in diagnosed patients. The number of imaging studies performed per patient was also fewer in misdiagnosed patients than in diagnosed patients (0.82±0.81 vs. 1.53±0.52, p<0.001). However, there was no significant difference in in-hospital mortality (18% vs. 15%, p=0.520). Multivariate analysis showed that the strongest predictor of misdiagnosis was walk-in mode of admission (odds ratio 4.777; 95% confidence interval 1.267–18.007; p=0.021).Both diversity of symptoms and variability of the severity of symptoms, especially walk-in mode of admission lead ER physicians to miss AAD in about 1 in 6 cases of AAD. It is therefore important to keep AAD as a differential diagnosis in mind, even when patients present with mild enough symptoms that allow them to walk into the ER.