We evaluated the impact of prophylactic nitroglycerin on the incidence of perioperative myocardial ischemia in patients with known or suspected coronary artery disease who undergo noncardiac surgery. Our goals were to better define the role of nitroglycerin in the management of high-risk patients and to explore the mechanisms of perioperative myocardial ischemia. Patients were assigned randomly to either a control group (n = 23) or to receive 0.9 micrograms.kg-1.min-1 of intravenous nitroglycerin (n = 22). The diagnosis of myocardial ischemia was based on a review of Holter electrocardiogram (ECG) recordings. There was no difference in the incidence of ischemia between groups. Seven control patients (30%) and seven nitroglycerin patients (32%) exhibited ECG evidence of ischemia. The preponderance of myocardial ischemia occurred during emergence from anesthesia (of the 14 patients exhibiting ischemia, 12 did so at emergence). There was an acute increase in heart rate at the onset of ischemia in all patients exhibiting ischemia with 14 of 18 episodes associated with an increase of 20% or greater. The heart rate associated with the onset of ischemia was greater in the nitroglycerin-treated patients than in the control group. We also found that the occurrence of myocardial ischemia on a preoperative Holter recording was strongly predictive of the subsequent occurrence of perioperative ischemia. In conclusion, the addition of nitroglycerin to standard anesthetic management of these high-risk patients does not measurably reduce perioperative ischemia.