Most cardiopulmonary diseases share at least one symptom with pulmonary embolism (PE). The aim of this study was to identify the most common acute causes of dyspnea, chest pain, fainting or palpitations, which diagnostic procedures were performed and whether clinicians investigate them appropriately. An Italian multicenter collaboration gathered 17,497 Emergency Department (ED) records of patients admitted from January 2007 to June 2007 in six hospitals. A block random sampling procedure was applied to select 800 hospitalised patients. Results of the overall 17,497 patients were obtained by weighting sampled cases according to the probability of the randomisation block variables in the whole population. The case-mix of enrolled patients was assessed in terms of cardiopulmonary symptoms, and the prevalence of acute disorders. The actual performance of procedures was compared with a measure of their accuracy as expected in the most common clinical presentations. PE occurred in less than 4% of patients with cardiopulmonary symptoms. Acute heart failure, pneumonia and chronic obstructive pulmonary disease exacerbation were the most likely diagnoses in patients with dyspnea. Acute myocardial infarction was present in roughly 10% of patients with chest pain. Atrial fibrillation was the prevalent diagnosis in patients with palpitations. Echocardiography, computed tomographic pulmonary angiography, perfusion lung scan, D-dimer test and B-type natriuretic peptide were performed less than expected from their accuracy. Diagnostic strategies, starting from non-specific symptoms and coping with the eventuality of PE, are likely to benefit from an increased awareness of the examination's accuracy in discriminating among several competing hypotheses, rather than in testing the single PE suspicion.