Reoperation for structural valve deterioration (SVD) of bioprosthetic mitral valves carries a presumed high operative risk, and transcatheter mitral valve-in-valve implantation has emerged as an alternative. However, surgical risk and long-term outcome following mitral valve re-replacement in these patients remain ill-defined. Hence, we sought to evaluate outcomes and long-term survival following surgical mitral valve re-replacement and to identify risk factors for mortality. From January 1990 to January 2017, 525 patients underwent surgical mitral valve re-replacement at Cleveland Clinic for bioprosthetic SVD: 133 (25%) isolated operations and 392 (75%) with concomitant procedures. Surgical complications and modes of death were compiled, long-term mortality assessed, and risk factors identified using a multivariable nonproportional hazards model and random forest analysis. SVD was characterized by bioprosthetic regurgitation in 81% (425 out of 525) and stenosis in 44% (231 out of 525). One in-hospital death occurred after isolated valve re-replacement (0.75%) and 28 deaths occurred (7.1%; P = .003) after nonisolated re-replacement, 19 (68%) of which were from coagulopathy, vasoplegia, and multisystem organ failure. In the nonisolated group, incremental risk factors for time-related death after re-replacement included New York Heart Association functional class IV symptoms, concomitant coronary artery bypass grafting, prolonged cardiopulmonary bypass time, and transfusions. Mitral valve re-replacement for bioprosthetic SVD was associated with low surgical risk and excellent long-term survival. Isolated mitral valve re-replacement for bioprosthetic SVD had near-zero surgical risk. Excessive cardiopulmonary bypass duration and multiple transfusions correlated with increased early mortality in nonisolated procedures, as did preoperative severe heart failure. Optimal surgical plan and timing of surgery are keys to success.