Objectives To compute left ventricular (LV) twist from 3-dimensional (3D) echocardiography. Background LV twist is a sensitive index of cardiac performance. Conventional 2-dimensional based methods of computing LV twist are cumbersome and subject to errors. Methods We studied 10 adult open-chest pigs. The pre-load to the heart was altered by temporary controlled occlusion of the inferior vena cava, and myocardial ischemia was produced by ligating the left anterior descending coronary artery. Full-volume 3D loops were reconstructed by stitching of pyramidal volumes acquired from 7 consecutive heart beats with electrocardiography gating on a Philips IE33 system (Philips Medical Systems, Andover, Massachusetts) at baseline and other steady states. Polar coordinate data of the 3D images were entered into an envelope detection program implemented in MatLab (The MathWorks, Inc., Natick, Massachusetts), and speckle motion was tracked using nonrigid image registration with spline-based transformation parameterization. The 3D displacement field was obtained, and rotation at apical and basal planes was computed. LV twist was derived as the net difference of apical and basal rotation. Sonomicrometry data of cardiac motion were also acquired from crystals anchored to epicardium in apical and basal planes at all states. Results The 3D dense tracking slightly overestimated the LV twist, but detected changes in LV twist at different states and showed good correlation (r = 0.89) when compared with sonomicrometry-derived twist at all steady states. In open chest pigs, peak cardiac twist was increased with reduction of pre-load from inferior vena cava occlusion from 6.25° ± 1.65° to 9.45° ± 1.95°. With myocardial ischemia from left anterior descending coronary artery ligation, twist was decreased to 4.90° ± 0.85° (r = 0.8759). Conclusions Despite lower spatiotemporal resolution of 3D echocardiography, LV twist and torsion can be computed accurately.