Left atrial (LA) enlargement is a negative prognostic factor for survival in patients with stroke, congestive heart failure, and myocardial infarction. In the absence of mitral valvular disease it is also a marker of chronic elevated left ventricular filling pressures. The aim of our study was to examine whether the currently considered factors such as demographic, clinical, and Doppler parameters fully correspond to LA maximal volume measured by real time three-dimensional echocardiography (RT3DE). Two-hundred-twenty-four patients (age 58+/-12 years) were studied. Of these, 66 were healthy volunteers and 158 were patients with more than 2 cardiovascular risk factors (109), documented coronary heart disease (CHD) and normal LV function (33), and patients with (10) and without (6) IHD and LV systolic dysfunction. Two-dimensional Doppler and tissue Doppler (TDI) echocardiographic parameters and LA maximal volume, assessed by RT3DE were analyzed. LA maximal volume values were positively and highly significantly associated, after adjustment for age and sex, with LV mass, mitral flow peak E velocity and E/A ratio, TDI E'/A' ratio and E/e' ratio (P<0.001). There were highly significant inverse associations of LA maximal volume and ejection fraction and peak A' velocity detected by TDI (P<0.0001). LA maximal volume was significantly correlated with the progression of diastolic dysfunction from normal to grade III. In particular, there was a clear difference between the normal and pseudonormal filling patterns (p<0.001) in terms of LA maximal volume. In conclusion, progressive LA volume increase is directly correlated with age, LV mass, and LV diastolic dysfunction, and inversely correlated with LV systolic function.