Background Isolated mechanical tricuspid valve replacement (mTVR) is uncommon, early mortality is reported to be high, and little is known regarding the long-term outcome. We sought to evaluate the long-term outcome of mTVR. Methods From 1980 to 2007, isolated mTVR was performed in 64 patients (33 men) at our institution; the median age was 45.5 years (6-71 years). There were 2192 tricuspid valve (TV) repairs and 137 isolated bioprosthetic TV replacements during the same time interval. Valve dysfunction was caused by congenital TV abnormality in 45 patients (70%), carcinoid heart disease in 13 (20%), traumatic TV regurgitation in 3 (5%), and other reason in 3 (5%). Twenty-three patients (36%) had at least 1 previous cardiac procedure (TV repair in 8 and bioprosthetic TV replacement in 7). Results Mechanical prostheses used included Starr-Edwards (before 1993) in 36 patients (56%) and bileaflet prostheses in 28 (44%). Concomitant procedures included atrial septal defect closure in 28 (44%), arrhythmia surgery in 11 (17%), and pulmonary valvectomy for carcinoid disease in 10 patients (16%). Early mortality occurred in 5 patients (7.8%). Early morbidity included a permanent pacemaker in 9 (14%) and reexploration for bleeding in 2 patients (3%). Mean follow-up was 6 years (maximum 22.4 years). Five- and 10-year survival was 65% and 58%, respectively. There was no valve-related mortality. Late morbidity included valve thrombosis in 5 patients (8%); 3 were managed nonoperatively and 2 underwent TV rereplacement. Conclusions Isolated mTVR still leads to increased early mortality. A mechanical valve can be considered in select situations when anticoagulation is necessary and in the presence of good right ventricular function.