A novel system for fusing 3-D echocardiography data sets from complementary acoustic windows was evaluated in 12 healthy volunteers and 12 patients with heart failure. We hypothesized that 3-D fusion would enable 3-D echocardiography in patients with limited acoustic windows. At least nine 3-D data sets were recorded, while three infrared cameras tracked the position and orientation of the transducer and chest respiratory movements. Corresponding 2-D planes of the fused 3-D data sets and of single-view 3-D data sets were assessed for image quality and compared with measurements of left ventricular function obtained with contrast 2-D echocardiography. The signal-to-noise ratio in accurately fused 3-D echocardiography recordings improved by 55% in systole (p < 0.001) and 47% in diastole (p < 0.00001) compared with the apical single-view recordings. The 3-D data sets acquired during short breath holds were successfully fused in 11 of 12 patients. The improvement in endocardial border definition (from 11.7 § 6.0 to 24.0 § 3.3, p < 0.01) enabled quantitative assessment of left ventricular function in 10 patients, with no significant difference in ejection fraction compared with contrast 2-D echocardiography. In patients with heart failure and limited acoustic windows, the novel fusion protocol provides 3-D data sets suitable for quantitative analysis of left ventricular function.