We evaluated 44 consecutive patients who underwent standard two-dimensional (2D) and live three-dimensional (3D) transthoracic echocardiography (TTE), as well as left heart catheterization with left ventriculography. Mitral regurgitant vena contracta area (VCA) was obtained by 3D TTE by systematic and sequential cropping of the acquired 3D TTE data set. Assessment of mitral regurgitation (MR) by ventriculography was compared to measurements of VCA by 3D TTE and to 2D TTE measurements of MR jet area to left atrial area (RJA/LAA), RJA alone, vena contracta width (VCW), and calculated VCA. VCA from 3D TTE closely correlated with angiographic grading (rs = 0.88) with very little overlap. VCA of <0.2 cm2 correlated with mild MR, 0.2-0.4 cm2 with moderate MR, and >0.4 cm2 with severe MR by angiography. Ventriculographic grading also correlated well with 2D TTE measurements of RJA/LAA (rs = 0.79) and RJA alone (rs = 0.76) but with more overlap. Assessment of VCW and calculated VCA by 2D TTE agreed least with ventriculography (rs = 0.51 and rs = 0.55, respectively). Live 3D TTE color Doppler measurements of VCA can be used for quantitative assessment of MR and is comparable to assessment by ventriculography.