Study Objectives: To identify the optimal subset of two electrocardiographic (EGG) bads for monitoring of ischemic ST depression and elevation during coronary artery bypass grafting (CABG) surgery. Design: Prospective observational clinical study. Setting: University hospital cardiac surgery operating room. Patients: 120 patients undergoing primary surgery or reoperation for CABG. Interventions: All six ECG limb leads and a precordial matrix of four leads were recorded intraoperatively approximately every 3 minutes. The limb leads were placed on the torso in modified Mason-Likar positions. The precordial leads were placed at V-4, V-5, and one interspace below them. Measurements and Main Results: New ischemic 1 mm ST depression and elevation episodes were determined. Neu ST deviation episodes attributed to nonischemic causes such as cooling at the onset of cardiopulmonary bypass (CPB), defibrillation at the end of CPB, new cardiac conduction changes after CPB, and postoperative pericarditis were excluded. Fixed ST deviation that did not change by I mm in the perioperative period was also excluded. Leads V-5 and III constituted the best two-lead set. These leads recorded 15 of the 16 ischemic ST elevation episodes and all 8 ischemic ST depression episodes. One ST elevation episode was not recorded intraoperatively but was recorded in lead V-1 in the immediate postoperative EGG. Leads V-5 and II recorded 13 of the 16 ischemic ST elevation episodes and all 8 ischemic ST depression episodes. Lead V-5 alone missed 8 episodes of ischemic ST elevation and one episode of ischemic ST depression. Conclusions: For monitoring of ischemia during CABG, leads V-5 and III are preferable to other two-cad sets, including the commonly used V-5 and II. No single lead is adequate. Lead V-5 alone missed approximately one half the episodes of ST elevation that were recorded by lead III or another inferior lead.