Chordal cutting targeting leaflet tethering has been described to improve the efficiency of annuloplasty during ischemic mitral regurgitation surgery. Histotripsy is an ultrasound based technique for tissue fragmentation through the cavitation generated by a very intense ultrasonic pulse. In this study we investigate the feasibility of using histotripsy for chordal cutting to avoid cardiopulmonary bypass and invasive surgery in infarcted heart.Experiments were performed in vitro in explanted sheep heart (N=10) and in vivo in sheep beating heart (N=5, 40+/-4kg). In vitro, the mitral valve basal chordae was removed, fixed on a holder in a water tank. The ultrasound pulses were emitted from the therapeutic device (1- MHz focused transducer, pulses of 8μs duration, peak negative pressure of 17 MPa, repetition frequency of 100Hz) placed at a distance of 64mm. In vivo, we performed sternotomy and the device was applied on the thorax cavity which was filled out with water. We analysed MV coaptation and chordae by real time 3D echocardiography. The animals were sacrificed at the end of the procedure, for postmortem anatomical exploration of the heart.In vitro, all the basal chordae were completely cut. The mean procedure time was 5.5 (+/-1.7) minutes. The diameter of the chordae was the main criteria affecting the duration of procedure. In the sheep, central basal chordae of anterior leaflet were completely cut. The mean procedure time was 22 (+/-9) minutes. By echography, the sectioned chordae was visible and no mitral valve prolapse was found. All the postmortem anatomical exploration of hearts confirmed the section of the basal chordea. No additional lesions were objectified.Noninvasive ultrasound histotripsy succeed to cut mitral valve basal chordae in vitro and in vivo in beating heart. If positive, this will open the door of completely noninvasive technique for MV repair especially in case of ischemic or functional MR.