OBJECTIVE This prospective study tested whether the natriuretic peptides predict cardiac death among patients using beta-blocking therapy after an acute myocardial infarction (AMI). BACKGROUND Natriuretic peptides have provided prognostic information after AMI, but their predictive value has not been well established in the era of beta-blocker use. METHODS A series of 521 patients (mean age 61 +/- 10 years) with AMI was included in the study. The end points were total mortality and non-sudden and sudden cardiac death (SCD). Plasma concentrations of atrial natriuretic peptide (ANP), N-terminal atrial natriuretic propeptide (N-ANP), brain natriuretic peptide (BNP), and ejection fraction (EF) were analyzed before hospital discharge. The cardiac medication was optimized (e.g., adherence to beta-blocking therapy was 97% at discharge and 95% at one year after AMI). RESULTS During a mean follow-up of 43 +/- 13 months, total mortality was 11.5% (60/521), cardiac mortality was 6.3% (33/521), and 3.1% (16/521) experienced SCD. On univariate analysis, high levels of all measured peptides and low EF predicted the occurrence of non-SCD (p < 0.001 for all). Peptides and EF also predicted the occurrence of SCD (p < 0.05), with elevated BNP (>23.0 pmol/l) being the most powerful predictor (hazard ratio [HR] 4.4, 95% confidence interval [CI] 1.4 to 13.8; p = 0.01). After adjusting for clinical variables, only elevated BNP (HR 3.9, 95% CI 1.2 to 12.3, p = 0.02) and low EF (<40%) (p = 0.03) remained as significant predictors of SCD. CONCLUSIONS Natriuretic peptides retain their prognostic value in the beta-blocking era among survivors of AMI. Elevated BNP provides information on the risk of subsequent SCD, independent of clinical variables and left ventricular EF.