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Age-stratified cutpoints for aminoterminal pro-brain natriuretic peptide(NT-pro-BNP) concentrations are diagnostic in 83%of all subjects with acute dyspnea. This study analyzed subjects with NT-pro-BNP concentrations between the “rule-out”and “rule-in”cutpoints, the so-called natriuretic peptide gray zone. NT-pro-BNP concentrations, clinical characteristics, and 60-day mortality were studied in 1,256 acutely dyspneic patients from an international multicenter study. Of all subjects, 215 had gray-zone NT-pro-BNP concentrations, 116 of whom(54%) were diagnosed with heart failure(HF). Among these subjects, patients with HF were more likely to be older, to have a history of HF, to be in atrial fibrillation, and to have elevated troponin T concentrations compared with those without HF. In multivariate analysis, the use of loop diuretics on presentation(odds ratio[OR] 3.99, 95%confidence interval[CI] 1.58 to 10.1, p=0.003), paroxysmal nocturnal dyspnea(OR 4.50, 95%CI 1.31 to 15.4, p=0.02), jugular venous distention(OR 3.05, 95%CI 1.06 to 8.79, p=0.04), and the absence of cough(OR 0.18, 95%CI 0.06 to 0.52, p=0.001) were associated with a diagnosis of acute HF in gray-zone patients. Subjects with HF and diagnostically elevated NT-pro-BNP concentrations had the highest mortality rates, subjects without HF and NT-pro-BNP concentrations< 300 ng/L had the lowest mortality rates, and subjects with gray-zone NT-pro-BNP had intermediate outcomes, irrespective of their final diagnoses. Adding specific clinical information to NT-pro-BNP improves diagnostic accuracy in subjects with intermediate NT-pro-BNP concentrations. Mortality rates in subjects with intermediate NT-pro-BNP concentrations are lower than in those with NT-pro-BNP concentrations diagnostic for HF but are higher than in subjects with NT-pro-BNP concentrations less than the gray zone.