We compared 12-lead electrocardiograms (ECGs) derived with an improved transformation matrix from EASI leads and standard 12-lead ECGs in the detection of acute myocardial ischemia and old infarction (MI). For the ischemia test, we used ECGs of 40 patients recorded prior to and at peak inflation during percutaneous transluminal coronary angioplasty, and for old MI we used test ECGs of 382 non-MI subjects and of 472 patients with prior MI documented by enzyme findings. Two experienced ECG readers served as separate, independent standards for lead-set comparisons, and the Philips ECG analysis program also classified the ECGs. The results showed no significant differences between the two lead sets in the detection of acute inflation-induced ischemia or of old MI according to coding by the electrocardiographers or the computer program. No significant differences were found between the electrocardiographers and the lead sets for acute ischemia. Classification differences between the electrocardiographers were larger than those between the lead sets for acute and old MI and were significant for the latter (P <.001). A more detailed comparison of the lead sets suggested a possible need for modified old-MI criteria and optimization of ST classification thresholds for acute ischemic injury, specific for the EASI 12-lead ECG. We conclude that the EASI-derived 12-lead ECG deserves serious consideration as an alternative to the standard 12-lead ECG in emergency situations and for monitoring in acute-care setting.