Results of a randomized, single-blind study did not support the routine use of B-type natriuretic peptide (BNP) testing in all severely dyspneic patients in the emergency department. At two Australian teaching hospital emergency departments, 612 consecutive patients who presented with acute severe dyspnea from August 2005 to March 2007 were assigned through randomized numbers in a sealed envelope to receive BNP testing (n = 306) or no testing (n = 306). Although patients were blinded to the intervention, clinicians and evaluators of study endpoints were not. The main endpoints of the study were admission rates, length of hospitalization, and emergency department medications. Secondary endpoints were mortality and readmission rates. The groups did not differ significantly in hospital admission rates (85.6% for the BNP group vs 86.6% for the control group; difference, –1.0 percentage point; 95% confidence interval [CI], –6.5 to 4.5 percentage points; P = .73), length of admission (median, 4.4 days; interquartile range, 2 - 9 days vs 5.0 days; interquartile range, 2 - 9 days; P = .94), or treatment of patients in the emergency department. Area under the receiver-operating characteristic curve was 0.87 (95% CI, 0.83 - 0.91), indicating good test discrimination. Adverse events were not measured. Limitations of this study include severe dyspnea requiring hospitalization in most patients, suggesting lack of generalizability to patients with milder degrees of breathlessness; lack of stratification by clinician; study performed at only 2 academic centers in Australia, also limiting generalizability; slight excess of patients with a history of heart failure in the BNP group; 60% of patients with chronic obstructive pulmonary disease and lung disease causing right heart failure and pulmonary hypertension, which can elevate BNP; and inability to exclude the possibility that there might be subgroups that would benefit from the test.