Plasma triiodothyronine (fT3) is a strong predictor of adverse clinical outcomes in various clinical conditions. Since fT3 in patients with end-stage renal diseases (ESRD) is frequently reduced and is associated with inflammation and cardiovascular damage, we prospectively tested the hypothesis that it predicts death in a cohort of 200 hemodialysis patients. Plasma fT3 was lower in ESRD patients (P<0.001) than in healthy subjects and in clinically euthyroid patients with normal renal function. During the follow-up 102 patients died. Patients who died had significantly lower plasma fT3 than those who survived (P<0.001) and in a Kaplan-Meyer analysis plasma fT3 was associated with death (P<0.001). On multivariate Cox's regression analyses, adjusting for a series of traditional and emerging risk factors including inflammation markers, patients with relatively higher plasma fT3 (hazard ratio (HR) (1 pg/ml increase in fT3)) had a 50% reduction in the risk of death (HR=0.50, 95% CI: 0.35-0.72) as compared to those having relatively lower fT3 levels. Of note, plasma fT3 captured most of the predictive power of interleukin-6 (IL-6) because this latter variable emerged as a significant predictor of death only in a model excluding fT3. Low fT3 is an independent predictor of death in hemodialysis patients. These data lend support to the hypothesis that thyroid dysfunction is implicated in the high risk of the ESRD population.