Experimental and clinical studies have shown the beneficial effects of triiodothyronine (T<sub>3</sub>) following myocardial revascularization on cardiopulmonary bypass (CPB). In this study, open-label T<sub>3</sub> was administered to 68 high-risk patients undergoing open heart surgery. The New Jersey Risk Assessment was used to calculate the preoperative estimated surgical mortality. A loading dose of T<sub>3</sub> was administered: (a) at release of the aortic cross-clamp, (b) whenever the patient became CPB dependent, (c) if the patient exhibited low cardiac output after discontinuing CPB and (d) as pretreatment before initiating CPB. All therapeutic modalities were followed by a continuous T<sub>3</sub> infusion. Following T<sub>3</sub> therapy, CPB was discontinued in all patients. Based upon discriminant analysis, a total of 26 deaths were expected from the entire group, but only 7 patients died, therefore, the observed mortality was reduced by 72% (p < 0.007). The use of T<sub>3</sub> had a major impact on reducing surgical mortality, and may be advocated as a new therapeutic modality in patients with high estimated mortality undergoing open heart surgery.