Background Pulmonary embolism (PE) is often mistaken as acute coronary syndromes (ACS) because of the considerable overlap in their clinical features.We evaluated the factors causing misdiagnosis of PE as ACS and factors that differentiate PE from ACS to improve the diagnosis efficacy of PE.Methods The medical records of 22 consecutive PE patients,between 2001 and 2010,who were initially suspected of ACS were retrieved.ACS was ruled out by coronary artery angiography before a definite diagnosis of PE was given.Twenty-two contemporary cases of ACS matched by age and sex were recruited as controls.Clinical manifestations,electrocardiograms (ECG),and biomarkers of these patients were reviewed retrospectively.The factors causing misdiagnosis of PE as ACS and factors differentiating PE from ACS were evaluated.Results We found two leading causes of misdiagnosis of PE as ACS.One is that PE can resemble ACS in several clinical aspects (symptoms and signs,ECG findings,plasma cardiac troponin I,and D-dimer).The other is the insufficient recognition of PE by clinicians.Risk factors for venous thromboembolism (VTE),especially deep venous thrombosis (DVT),together with signs of PE,such as unexplained dyspnea or hypoxemia,and right ventricular pressure overload on ECGs are valuable in differentiating the two diseases.Conclusions Differentiation between PE and ACS is sometimes challenging.Adequate awareness of the risk factors for VTE and the signs of PE are crucial in the diagnosis of PE.