Twelve-lead ST-segment monitoring is a widely used tool for capturing focal ischemia and transient intermittent episodes. However, continuous registration of all 10 electrodes is impractical in clinical settings. This study investigated the accuracy of 2 derived 12-lead strategies that required 6 electrodes, including all limb leads, and 2 precordial leads by using population-based (generalized) and individualized (patient-specific) reconstruction coefficients to derive the additional 4 chest leads. A total of 26,880 simultaneous digital conventional 12-lead generalized and patient-specific electrocardiograms were monitored over 112 hours in 39 patients during percutaneous coronary intervention, including 159 balloon occlusions in 63 arteries, to test accuracy at rest and during ischemia. Occlusion duration was 78 seconds (range 42 to 96) in the left main coronary in 2 patients, the left anterior descending artery in 15, the right coronary artery in 10, the circumflex artery in 2, and graft segments in 5 patients. Average summated 12-lead ST deviation over the study population at baseline was 377 microV (range 104 to 1,718), which increased at peak ischemia to an average of 1,086 microV (range 282 to 4,099). Median absolute differences at peak ischemic ST deviation were 25 microV in lead V(1), 0 microV in lead V(2), 35 microV in lead V(3), 34 microV in lead V(4), 0 microV in lead V(5), 11 microV in lead V(6), and 114 microV for summated 12-lead ST deviation with the generalized method and 7 microV in lead V(1), 4 microV in lead V(2), 1 muV in lead V(3), 5 microV in lead V(4), 4 microV in lead V(5), 9 microV in lead V(6), and 83 microV for the summated 12-lead ST deviation with the patient-specific method. Limb leads (I, II, III, aVR, aVL, and aVF) were identical in all patients. Thus, generalized and patient-specific methods derived from 12-lead electrocardiography using actual limb and 2 precordial electrodes accurately derived the additional chest leads at rest and during ischemia. These approaches appear to be more practical than conventional 10-electrode monitoring but preserve high accuracy.