We investigated the clinical value of three-dimensional (3D) transesophageal echocardiography (TEE) color flow Doppler (TEE-CFD) for percutaneous transcatheter closure of mitral valve prosthesis paravalvular leaks (PVLs) compared to two-dimensional (2D) TEE. The number, location, and size of the mitral valve prosthesis PVLs were determined in 8 patients using 2D and 3D TEE-CFD. We also evaluated 2D and 3D TEE-CFD for identifying the canalization of the target PVL during the intervention and assessing the change in the PVL effective orifice after the endovascular procedure. We visualized 12 PVLs using 2D TEE-CFD and 15 PVLs using 3D TEE-CFD. No substantial disagreement was found between 2D and 3D TEE-CFD for the location for each of the PVLs. No difference was found in the vena contracta short axis width obtained by 2D TEE-CFD and 3D TEE-CFD (5.7 ± 1.4 mm vs 5.5 ± 1.3 mm, respectively, p = 0.09). However, only 3D TEE-CFD demonstrated the effective circumferential orifice length of the PVL (12.2 ± 8.5 mm). A closure device was deployed in 6 cases. In 1 case, the canalization of a nontarget PVL, visualized only on 3D TEE-CFD, led to an appropriate change in the treatment strategy. The reduction in the mean PVL vena contracta width demonstrated using 2D TEE-CFD and 3D TEE-CFD was similar (2.2 ± 0.7 mm vs 2.1 ± 1.1 mm, respectively, p = 0.69). However, only 3D TEE-CFD verified the reduction of the effective orifice circumferential length of the PVL by 10.5 ± 5.6 mm. In conclusion, 3D TEE-CFD provided unique and additive information in patients with mitral valve prosthesis PVLs. This new technology has the potential to improve the procedural success of percutaneous transcatheter closure of PVLs.