In clinical heart transplantation, the heart is procured from brain dead (BD) organ donors who acutely experienced a variety of critical illnesses. In all of these conditions, a profound derangement of the thyroid profile has been observed. Although the plasma levels of thyroid stimulating hormone (TSH) remain unchanged, there is a rapid decline in free triiodothyronine (FT3) levels (p < 0.0001) as well as an elevation of reverse triiodothyronine (rT3) (p < 0.001). Following induction of experimental brain death, the heart exhibits a progressive significant hemodynamic-biochemical deterioration (reduction of cardiac contractility, depletion of high energy phosphates, glycogen, and accumulation of tissue lactate). The administration of T3 to BD animals resulted in rapid reversal of the hemodynamic and metabolic derangements. The impact of T3 therapy to unstable human brain dead organ donors has resulted in rapid hemodynamic stability allowing significant reduction of inotropic support (p < 0.001). These hearts, following cardiac transplantation, exhibited excellent hemodynamic function in the recipients. The low FT3 state has also been observed during and following open heart surgery on cardiopulmonary bypass (CPB). Therefore, at the completion of the heart transplant procedure, T3 was also administered to the recipient to prevent relapse of the hemodynamic-metabolic abnormality observed in the donor. The impact of T3 therapy to initially unstable donors allowed for rapid inotropic reduction and recovery of the heart, thus enlarging the donor organ pool and improving the outcome of the recipients following cardiac transplantation.