B-type natriuretic peptide (BNP) and early diastolic transmitral velocity/tissue Doppler mitral annular velocity (E/Ea) both estimate left ventricular filling pressure, but have not been compared in the diagnosis of congestive heart failure (CHF). One hundred twenty-two hospital inpatients with suspected CHF underwent simultaneous clinical examination, BNP measurement, and comprehensive echo-Doppler examination. The accuracy of BNP and echocardiography was compared with the Framingham criteria diagnosis of CHF. Seventy patients (57%) had clinical CHF, whereas 52 (43%) did not. In all patients, the optimal BNP cutoff was >250 pg/ml (sensitivity 86%, specificity 77%). E/Ea >15 had 83% sensitivity and 82% specificity, whereas comprehensive echo-Doppler had 95% sensitivity and 88% specificity for CHF. In patients with normal ejection fraction, the optimal BNP cutoff was >150 pg/ml (sensitivity 79%, specificity 85%). E/Ea >15 had 79% sensitivity and 93% specificity, whereas comprehensive echo-Doppler had 85% sensitivity and 96% specificity for CHF. In patients with reduced ejection fraction, the optimal BNP cutoff was >300 pg/ml (sensitivity 88%, specificity 60%). E/Ea >15 had 92% sensitivity and 72% specificity, whereas comprehensive echo-Doppler had 96% sensitivity and 80% specificity (p = 0.08 compared with BNP) for CHF. Overall, BNP and E/Ea have similar diagnostic accuracy for CHF in this patient population. In patients with reduced ejection fraction, comprehensive echo-Doppler trended toward higher specificity than BNP for clinical CHF.