BACKGROUND Echocardiographic indices of cardiac structure and function and natriuretic peptide levels are strong predictors of mortality in patients with heart failure. Whether cardiac ultrasound and natriuretic peptides provide independent prognostic information is uncertain. METHODS Echocardiograms and measurements of N-terminal pro-brain natriuretic peptide (NT-proBNP) were prospectively performed in 211 patients with left ventricular systolic dysfunction who were followed for a median of 4 years. Echocardiographic variables and NT-proBNP were examined as predictors of all-cause mortality in univariable and multivariable proportional hazards models. RESULTS Participants averaged 57 years old (SD 12 years) and had a mean left ventricular ejection fraction of 32% (SD 11%). A total of 71 patients (34%) died during the follow-up period. N-terminal pro-brain natriuretic peptide was a strong predictor of mortality (P < .001) as were multiple echocardiographic measures. In models that included age and NT-proBNP, with other clinical variables eligible for entry by stepwise selection, significant predictors of death included left ventricular ejection fraction (P = .013) and end-diastolic volume (P < .001), left atrial volume index (P = .005), right atrial volume index (P = .003), and tricuspid regurgitation area (P = .015). In models that also included left ventricular ejection fraction, end-diastolic volume of the left ventricle (P = .019), left atrial volume (P = .026), and right atrial volume (P = .020) remained significant predictors of mortality. CONCLUSIONS Left ventricular size and function and left atrial and right atrial sizes are significant predictors of all-cause mortality in patients with heart failure, independent of NT-proBNP levels and other clinical variables.