Echocardiography is frequently used for sequential evaluation of left ventricular (LV) function, although the reproducibility of such conventional measurements as LV ejection fraction (EF) have been questioned. The utility of such newer measurements as tissue Doppler imaging and left atrial (LA) size in serial clinical testing are undefined. The magnitude and clinical relevance of changes in conventional and new measurements of LV function were investigated and compared in 346 consecutive patients undergoing sequential echocardiography. Change in LA area, LVEF, tissue E velocity (Em), and transmitral E to Em ratio (E/Em) were compared over 304 ± 239 days. Changes within and between parameters (after mean correction to make measurements comparable) were assessed in groups designated as stable (n = 144) or unstable (n = 202) according to clinical progress. A single observer remeasured these parameters in stable patients individually and with paired studies side by side. Significant variability was seen in all measurements, with change in LVEF the only parameter differing between stable and unstable groups (6.4 ± 8.9% vs 9.4 ± 5.4%; p <0.001). Tissue Em and E/Em ratio were more variable than LA area or LVEF. In stable patients, LVEF changed the least and E/Em changed the most over time (p <0.05). With a single blinded observer, Em had improved reproducibility (1.5 ± 1.9 vs 2.3 ± 2.6 cm/s; p <0.001), as did visual EF. In conclusion, variability in all measurements was high irrespective of clinical status. Newer measurements were no better than LVEF in detecting changes in clinical status. Sequential LV assessment should be interpreted with caution, and more robust measurements are needed.