We report a case in which replacement of a low-profile porcine Liotta bioprosthesis was required 21 years after initial implantation. The patient underwent mitral valve replacement with a 28-mm Liotta bioprosthesis in 1985 for mitral stenosis. Twenty-one years later, severe mitral regurgitation was detected at echocardiography and mitral valve reoperation combined with tricuspid annuloplasty was successfully performed. Focal perforation of two cusps with consequent intravalvular leak on bioprosthesis was found. This is the longest durability report for a Liotta bioprosthesis in mitral position.