Background: Amino (N)-terminal pro-brain natriuretic peptide (NT-proBNP) testing is useful for diagnostic and prognostic evaluation in patients with dyspnea. An inverse relationship between body mass index (BMI); (calculated as weight in kilograms divided by height in meters squared) and NT-proBNP concentrations has been described. Methods: One thousand one hundred three patients presenting to the emergency department with acute dyspnea underwent analysis. Patients were classified into the following 3 BMI categories: lean (<25.0), overweight (25.0-29.9), and obese (≥30.0). Results: The NT-proBNP concentrations in the overweight and obese groups were significantly lower than in the lean patients, regardless of the presence of acute heart failure (P<.001). The positive likelihood ratio for an NT-proBNP-based diagnosis of acute heart failure was 5.3 for a BMI lower than 25.0, 13.3 for a BMI of 25.0 to 29.9, and 7.5 for a BMI of 30.0 or higher. A cut point of 300 ng/L had very low negative likelihood ratios in all 3 BMI categories (0.02, 0.03, and 0.08, respectively). Among decedents, the NT-proBNP concentrations were lower in the overweight and obese patients compared with the lean subjects (P<.001). Nonetheless, a single cut point of 986 ng/L strongly predicted 1-year mortality across the 3 BMI strata, regardless of the presence of acute heart failure (hazard ratios, 2.22, 3.06, and 3.69 for BMIs of <25.0, 25.0-29.9, and ≥30.0, respectively; all P<.004); the risk associated with a high NT-proBNP concentration was detected early and was sustained to a year after baseline in all 3 BMI strata (all P<.001). Conclusions: In patients with and without acute heart failure, the NT-proBNP concentrations are relatively lower in overweight and obese patients with acute dyspnea. Despite this, the NT-proBNP concentration retains its diagnostic and prognostic capacity across all BMI categories. ©2007 American Medical Association. All rights reserved.