Background Morbidity and mortality limit surgical mitral annuloplasty in patients with ischemic mitral regurgitation(IMR). A percutaneous transvenous mitral annuloplasty(PTMA) approach for mitral valve repair was evaluated by placing a novel implantable device in the coronary sinus(CS) of sheep with chronic IMR. Methods and Results Three sheep developed IMR 6 weeks after induced posterior myocardial infarction. An annuloplasty device was implanted percutaneously through the right internal jugular vein in the CS. Mitral annular anterior-posterior(A-P) and MR jet area were assessed by real-time 3D echocardiography with 3D software. With the annuloplasty device in place, the A-P dimension was reduced from 2.5 cm to 1.9 cm ( P<0.05). Mitral annular A-P dimension in mid-systole decreased by 24.0% at postprocedure and was maintained by 28.0% at 4 weeks follow-up. Mitral regurgitation was reduced from 1-2+ to 0 in two sheep. There were no episodes of coronary sinus perforation or coronary artery occlusion during the procedure and follow-up. The device migration occurred in one sheep at immediate post-procedure. Conclusions Percutaneous coronary sinus–based mitral annuloplasty using a novel implantable device was effective in mitral annular A-P dimension and safe in an ovine model with chronic IMR. Device failure resulting from migration of the implant limits assessment of efficacy.