The technique of warm heart surgery is defined as continuous warm blood cardioplegia and normothermic cardiopulmonary bypass. Although the systemic effects of traditional myocardial protection are well known, the effects of warm heart surgery are not. In a prospective trial, 204 patients undergoing coronary artery bypass grafting were randomized to the warm heart surgery technique (normothermic group) or traditional intermittent cold blood cardioplegia and cardiopulmonary bypass (hypothermic group). The groups had similar heparin sodium requirements, activated clotting times, urine output, hematocrit, and blood product utilization. There were no differences in hemodynamics immediately after cardiopulmonary bypass. The normothermic patients had a higher incidence of spontaneous defibrillation at cross-clamp removal (84%) than the hypothermic patients (33%) (p < 0.01). An increase in the flow rate of low K+ cardioplegia was necessary to eradicate electrical activity during aortic occlusion more often in the normothermic patients (20%) than in the hypothermic patients (3%) (p < 0.01). When low K+ cardioplegia was ineffective, high K+ cardioplegia was necessary to eradicate electrical activity in 31% of the normothermic patients compared with 10% of the hypothermic patients (p < 0.05). The total cardioplegia volume delivered to the normothermic group (4.7 +/- 1.9 L) was higher than that delivered to the hypothermic group (2.6 +/- 0.8 L) (p < 0.01). Although urine output was similar in both groups, the serum K+ levels were higher in the normothermic group (5.7 +/- 0.8 mmol/L) than in the hypothermic group (5.3 +/- 0.8 mmol/L) (p < 0.001). Low systemic vascular resistance during normothermic cardiopulmonary bypass resulted in the infusion of significantly higher volumes of crystalloid solutions (3,650 +/- 800 mL) and more phenylephrine hydrochloride (1.3 +/- 2.2 mg) than during hypothermic cardiopulmonary bypass (3,100 +/- 700 mL and 0.4 +/- 0.6 mg, respectively) (p < 0.01). Warm heart surgery should be used with caution in patients with renal failure or severe cerebrovascular disease. Serum K+ levels and fluid overload must be carefully monitored during long operations. The high incidence of low systemic vascular resistance and resulting phenylephrine infusion during normothermic cardiopulmonary bypass raises concerns about possible mammary artery or coronary artery spasm and the risk of stroke.