Three-dimensional echocardiography (3DE) makes it possible to capture the entire heart in a single data set that theoretically could be used to extract any two-dimensional (2D) views and potentially replace the standard practice of serial 2D acquisitions. The aim of this study was to test the hypothesis that the quality of 3DE-derived 2D images is sufficient to allow the visualization of the left ventricular (LV), right ventricular (RV), and left atrial (LA) endocardium, on par with images from conventional two-dimensional echocardiography (2DE), and potentially more accurate quantification of chamber size and function. First, the investigators prospectively studied 36 patients who underwent 2DE in 14 standard views, and full-volume data sets from 3DE, from which the same views were extracted offline. The ability to visualize the LV endocardium, RV free wall, and LA endocardium was scored. LV linear dimensions, LV volumes, and LV ejection fraction (LVEF), LA volume, and RV basal dimension were measured and compared between both types of images. Thereafter, 40 patients who underwent 2DE, 3DE, and cardiac magnetic resonance (CMR) imaging on the same day were retrospectively studied. LV volumes and LVEF derived from 2DE and 3DE were compared side by side against the CMR reference. Intertechnique agreement in visualization scores was 87% for LV segments, 86% for the RV free wall, and 83% for the LA endocardium. The correlations between 2DE- and 3DE-derived measurements were 0.95, 0.97, and 0.97 for LV volumes and LVEF, respectively, and 0.88 for RV basal dimension. Three-dimensional echocardiography-derived measurements of LV volumes and LVEF were more similar to those on CMR than those obtained on conventional 2DE. The feasibility of segmental assessment of cardiac chambers using 3DE-derived 2D views is similar to that using conventional 2DE. This approach provides similar quantitative information, including more accurate LV volumes and LVEF measurements compared with CMR, and thus promises to significantly shorten the duration of the echocardiographic examination.