Preoperative factors associated with increased mortality and worse outcome after tricuspid valve replacement in patients with severe tricuspid regurgitation are poorly understood. We retrospectively analyzed 189 patients (37% men; age, 67.5±11.3 years) who underwent tricuspid valve replacement for severe tricuspid regurgitation. Operative mortality rate was 10%, and was associated with intra-aortic balloon pump (odds ratio, 3.2; 95% confidence interval, 1.9 to 5.6; P<0.0001) or the presence of severe symptoms (New York Heart Association class IV relative to classes II and/or III) at the time of surgery (1.7; 95% confidence interval, 1.05 to 2.8; P=0.02). At the end of follow-up (29.3±27.1 months), 70 patients (37%) died, 6 (3%) needed tricuspid reoperation, and 41 (21.7%) were readmitted for heart failure. Seventy-eight patients (41.3%) were free from cardiovascular events (death, tricuspid reoperation, or heart failure admissions). The only echocardiographic parameter independently associated with adverse outcomes was a decrease in the right index of myocardial performance ratio. All-cause mortality was independently associated with a higher Charlson index (hazard ratio, 1.18; 95% confidence interval, 1.01 to 1.36; P=0.03), shorter right index of myocardial performance ratio (0.91; 95% confidence interval, 0.87 to 0.96; P=0.005), and preoperative New York Heart Association IV class (1.71; 95% confidence interval, 1.3 to 2.2; P<0.0001). In 68 patients with isolated tricuspid valve replacement, the associations between short right index of myocardial performance ratio, high Charlson index, New York Heart Association class IV, and increased mortality remained significant. Tricuspid valve replacement for severe tricuspid regurgitation can be performed with an acceptable operative mortality if patients undergo surgery before the onset of advanced heart failure symptoms. Late mortality is associated with a high preoperative Charlson index, short right index of myocardial performance ratio, and advanced New York Heart Association class.