A significant reduction (p < 0.0001) in plasma-free triiodothyronine (T3), which is known to have an inotropic effect, has been documented in patients undergoing open-heart procedures. To investigate the effect of this observation, 22 pigs underwent 2 hours (Group 1, r = 10) or 3 hours (Group 2, r = 12) of myocardial ischemia during cardiopulmonary bypass (CPB) at 26°C; the myocardium was protected by cardioplegic solution and cold saline solution at 30-minute intervals. After the pig was rewarmed to 37°C, CPB was discontinued, and measurements of hemodynamic function were made 10 and 70 minutes later. Half of the pigs (Subgroup B) received 6 μg of T3 intravenously immediately after removal of the aortic cross-clamp; the remainder (Subgroup A) received no T3. After 2 hours of ischemia, untreated pigs showed significantly reduced myocardial function 10 minutes after discontinuation of CPB. By 70 minutes after the end of CPB, 2 of 5 untreated pigs (Subgroup A) had died of low cardiac output, but all 5 treated pigs (Subgroup B) survived. After 3 hours of ischemia, both groups showed some reduced function at 10 minutes, though the reduction was more marked in untreated animals. By 70 minutes, 4 of 6 untreated pigs had died of myocardial failure and all treated pigs remained alive (p < 0.03). Surviving pigs in both groups still demonstrated some reduced function compared with values obtained before CPB. When all pigs are considered together, overall survival of those that did not receive T3 was significantly less than those that did (p < 0.006). T3 clearly has a significant beneficial inotropic effect when administered after a period of myocardial ischemia and CPB; its administration may be indicated in patients undergoing open-heart operations. © 1988, The Society of Thoracic Surgeons. All rights reserved.