A prospective study was performed to evaluate the diagnostic accuracy of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) levels, measured simultaneously in serum and pleural fluid, in identifying pleural effusions due to heart failure. Pleural fluid and serum samples from all patients presenting for thoracentesis between April 2004 and May 2005 were simultaneously collected. The discriminative properties of NT-proBNP levels in identifying pleural effusions due to heart failure were determined by receiver operating characteristic curve analysis and compared to the diagnostic value of finding a transudate by Light's criteria. Ninety-three patients were evaluated, 27% with cardiac effusion and 73% with exudative effusions of various cause. Levels of NT-proBNP in pleural fluid and serum correlated closely. Serum and pleural fluid NT-proBNP levels were significantly elevated in patients with cardiac effusion. With a cut-off value of 4,000 ng.L(-1), NT-proBNP levels in pleural fluid and serum displayed comparably high diagnostic accuracies of 92 and 91%, respectively. All patients misclassified by Light's criteria were correctly identified by measuring NT-proBNP levels. N-terminal-pro-B-type natriuretic peptide levels in either pleural fluid or serum showed a high diagnostic accuracy compared to traditional criteria. Thus measuring N-terminal-pro-B-type natriuretic peptide is a valuable additional diagnostic tool for the detection or exclusion of cardiac origin of pleural effusions.