The influence of type of prosthesis on the late outcome of patients with combined mitral-aortic valve replacement was analyzed by comparing, at a 14-year follow-up, patients receiving two biological prostheses (group 1; n = 135), two mechanical prostheses (group 2; n = 221), or a mechanical prosthesis in the aortic position and a bioprosthesis in the mitral position (group 3; n = 97). No difference was found among the three groups in terms of actuarial survival and incidence of and freedom from valve-related deaths, thromboemboli, and hemorrhages. Patients with biological prostheses had a significantly greater incidence of structural valve deterioration, reoperations, and overall complications when compared with patients with only mechanical prostheses. The results of an extended follow-up of patients with combined mitral-aortic valve replacement indicate that mechanical prostheses perform better in the long-term owing to their superior durability when compared with biological valves. The use of bioprostheses should be confined to old patients with limited life expectancy because of their cardiac disease, provided that anticoagulants are not used. Combination of mechanical and biological prostheses in the same patient should be avoided because the advantages of each type of prosthesis are lost.