The aim of the present investigation was to evaluate the diagnostic accuracy of brain natriuretic peptide (BNP) and amino terminal proBNP (NT-proBNP) for the detection of mild/moderate and severe impairment of left ventricular ejection fraction (LVEF). In 180 subjects BNP and NT-proBNP were measured by two novel fully automated chemiluminescent assays (Bayer and Roche methods). LVEF as determined by echocardiography was categorized as normal (> 60%), mildly/moderately reduced (35-60%) and severely diminished (< 35%). Discriminating between patients with LVEF< 35% (n = 32) and subjects with LVEF > or = 35% (n = 148), receiver-operating characteristic (ROC) curve analysis revealed an area under the curve (AUC) of 0.912 for BNP and of 0.896 for NT-proBNP (difference 0.016, p = 0.554). In contrast, BNP displayed an AUC of 0.843 and NT-proBNP an AUC of 0.927 (difference of 0.084, p = 0.034) when comparing patients with LVEF 35-60% (n = 37) and individuals with LVEF > 60% (n = 111). Evaluation of discordant false classifications at cut-off levels with the highest diagnostic accuracy showed advantages for BNP in the biochemical diagnosis of LVEF < 35% (4 misclassifications by BNP and 25 by NT-proBNP, p < 0.001) and for NT-proBNP in the detection of LVEF 35-60% (25 misclassifications by BNP and 7 by NT-proBNP, p = 0.002). In conclusion, the present study indicates a different diagnostic accuracy of BNP and NT-proBNP for the detection of mildly/moderately reduced LVEF and severely diminished LVEF. Advantages of BNP may be advocated for the biochemical diagnosis of more severely impaired LVEF, while NT-proBNP might be a more discerning marker of early systolic left ventricular dysfunction.