Objective: To evaluate N-terminal pro-brain natriuretic peptide (NT-proBNP) as a diagnostic and prognostic marker for systolic heart failure in the general population. Design: Study participants, randomly selected to be representative of the background population, filled in a heart failure questionnaire and underwent pulse and blood pressure measurements, electrocardiography, echocardiography, and blood sampling and were followed up for a median ( range) period of 805 ( 6021171) days. Setting: Participants were recruited from four randomly selected general practitioners and were examined in a Copenhagen university hospital. Patients: 382 women and 290 men in four age groups ( 50259 ( n = 174); 60269 ( n = 204); 70279 ( n = 174); greater than or equal to 80 years ( n = 120)). Main outcome measures: Value of NT-proBNP in evaluating patients with symptoms of heart failure and impaired left ventricular (LV) systolic function; prognostic value of NT-proBNP for mortality and hospital admissions. Results: In 38 ( 5.6%) participants LV ejection fraction ( LVEF) was less than or equal to 40%. NT-proBNP identified patients with symptoms of heart failure and LVEF ( 40% with a sensitivity of 0.92, a specificity of 0.86, positive and negative predictive values of 0.11 and 1.00, and area under the curve of 0.94. NT-proBNP was the strongest independent predictor of mortality ( hazard ratio (HR) = 5.70, p< 0.0001), hospital admissions for heart failure ( HR = 13.83, p< 0.0001), and other cardiac admissions ( HR = 3.69, p, 0.0001). Mortality ( 26 v 6, p = 0.0003), heart failure admissions ( 18 v 2, p = 0.0002), and admissions for other cardiac causes ( 44 v 13, p, 0.0001) were significantly higher in patients with NT-proBNP above the study median (32.5 pmol/l). Conclusions: Measurement of NT-proBNP may be useful as a screening tool for systolic heart failure in the general population.