The aim of this article was to study beat-to-beat QRS variability in patients with ischemia and old myocardial infarction using the 12-lead resting electrocardiogram (ECG). The variability analysis was based on beats that have been synchronized in time with an iterative alignment technique. The QRS variability was measured in patients submitted for myocardial scintigraphy. Those with a normal myocardial scintigraphy (called NO, n = 34, mean age 57 years, 23 women) were compared with a group with both myocardial infarction and exercise-induced ischemia (called ISCINF, n = 27, mean age 57 years, 5 women). The mean QRS variability was somewhat smaller in lead I in ISCINF than in NO, and there was no statistically significant difference in QRS variability among the groups in leads II, III, and V1-V6. Using a multivariate approach, the joint variability in leads I, II, II, and V1-V6 was used for calculating receiver operating characteristics based on a leave-one-out procedure. The sensitivity for detecting coronary artery disease was 75% at a specificity of 50%. It is concluded that beat-to-beat QRS variability in the 12-lead ECG does not discriminate between the presence and absence of coronary artery disease sufficiently well for clinical purposes.