N-terminal pro-brain natriuretic peptide (NTproBNP) correlates with left ventricular (LV) filling pressure. The ratio between early diastolic transmitral velocity and early mitral annular diastolic velocity (E/Ea) reflects LV filling pressure in a variety of cardiac diseases. However this relationship was not validated in some categories of patients. Our aim was to evaluate the correlation between tissue Doppler velocities of the mitral annulus and NTproBNP levels in sinus rhythm patients. Methods Echocardiography was performed in 111 consecutive patients simultaneously with NTproBNP measurement. E/Ea and E/(Ea × Sa) were calculated (Sa is the maximal systolic velocity of mitral annulus); the average of the velocities of septal and lateral mitral annulus was used. Results Simple regression analysis demonstrated a significant linear correlation between E/(Ea × Sa) and NTproBNP (r = 0.71, P < 0.0001), superior to E/Ea correlation (r = 0.58, P < 0.0001). Significant but weaker correlations were found between NTproBNP and Sa, pulmonary artery systolic pressure, Ea, mitral E/A (early/late diastolic transmitral velocity), E wave, mitral E deceleration time and LV ejection fraction (LVEF). The optimal E/(Ea × Sa) cut-off for prediction of NTproBNP levels > 900 pg/ml was 1.5 (sensitivity = 81%, specificity = 70%). Among analyzed parameters, E/(Ea × Sa) was best correlated with NTproBNP levels in patients with LVEF ≥ 50% (r = 0.80, P < 0.0001), with depressed LVEF (<50%) (r = 0.66, P < 0.0001), with regional wall motion abnormalities (r = 0.75, P < 0.0001), and with E/Ea 8 to 15 (r = 0.58, P < 0.0001). Conclusions E/(Ea × Sa) strongly correlates with NTproBNP, regardless of LVEF, and can be a simple and accurate echocardiographic index in patients in sinus rhythm, particularly in those with regional wall motion abnormalities or intermediate E/Ea.