Comparative assessment of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) across a wide spectrum of angiographic and clinical coronary artery disease (CAD) in a consecutive series of patients has not been reported. This study examined 879 subjects (684 patients who had angiographically proved CAD and 195 controls who did not have CAD). NT-pro-BNP concentrations were measured before an angiographic procedure that allowed diagnosis of CAD and measurements of left ventricular ejection fraction and end-diastolic blood pressure. Median values (25th and 75th percentiles) of NT-pro-BNP in patients and controls were 474.5 pg/ml (162.3 and 1,542.8) and 117.0 pg/ml (60.1 and 230.6), respectively (p <0.001). In patients who had stable angina, unstable angina, and acute myocardial infarction, NT-pro-BNP concentrations were 327.7 pg/ml (129.2 and 973.2), 660.6 pg/ml (201.2 and 1,563.5), and 1,045.0 pg/ml (323.8 and 2,486.0, p <0.001). NT-pro-BNP concentrations in subgroups with 1-, 2-, and 3-vessel CAD were 385.5 pg/ml (117.2 and 1,266.0), 463.0 pg/ml (135.0 and 1,480.5), and 533.8 pg/ml (221.8 and 1,809.4), respectively (p = 0.005). Multivariable analysis showed that NT-pro-BNP was an independent correlate of the presence of CAD (chi-square 10.8, odds ratio 1.08, 95% confidence interval 1.03 to 1.13 for 100-pg/ml increase in concentration; p <0.001), acute coronary syndromes (chi-square 6.3, odds ratio 1.01, 95% confidence interval 1.00 to 1.02 for 100-pg/ml increase in concentration, p = 0.01) and a strong trend that was independently associated with angiographic severity (chi-square 3.68, p = 0.055). This study shows that NT-pro-BNP concentrations are high across the entire spectrum of CAD and parallel the clinical or angiographic severity of CAD.