This study examines the outcomes of the cryopreserved mitral homograft in 110 patients prospectively followed with clinical, echocardiographic and structural valve deterioration (SVD) assessments.The etiology of mitral disease was: rheumatic disease (n = 70), endocarditis (n = 33), and others (n = 7). There were 31 partial homografts and 79 total homografts. Mitro-aortic homograft valve replacement was performed in 29 cases.Mean follow-up was 9.8 ± 6.3 years (up to 19.2 years). There were seven early (<3 months) and 13 late deaths. There have been nine early (<3 months) and 24 late reoperations. Postoperatively, nine patients had endocarditis and six had an ischemic event. As compared to baseline, follow-up echocardiography showed progression of MR grade (from 0.4 to 1.3 p < 0.001) with stenosis (elevated gradient: from 3.9 to 7.0 mmHg p < 0.001 and decreased valve area: from 2.3 to 1.7 cm(2) p < 0.001). The proportion of freedom from SVD was 90%, 76%, and 65% at five years, 10 years, and 15 years, respectively. SVD was more frequent in pregnant patients (p = 0.016 vs. no pregnancy) and in patients with a ring smaller than 30 mm. Stenosis related to SVD was more pronounced for age <40 years and ring size 30 mm. Mitral-aortic homograft valve replacement was the preferred choice in complex infective endocarditis. Pathological analysis of the explanted homografts almost invariably showed dense fibrosis with calcification and no cellularity.Mitral homografts have early echocardiographic results similar to those of valve repair. SVD produced mixed stenosis with insufficiency and its incidence was comparable to that of bioprosthetic SVD. An improvement in the preservation mode of valvular homografts is warranted.