BACKGROUND The 12-lead electrocardiogram (ECG) is a primary tool in the evaluation and risk stratification of patients with suspected acute myocardial infarction (AMI), even though the initial ECG of these patients is often normal or nondiagnostic. Myocardial ischemia induces depolarization changes that can be quantified by analysis of high-frequency QRS (HFQRS) components. We aimed to demonstrate the potential usefulness of HFQRS analysis in diagnosing myocardial ischemia by characterizing the morphological patterns of the HFQRS signals in patients with AMI before and following reperfusion. METHODS Five-minute high-resolution ECG was acquired from 30 patients with AMI (age 55 ± 11 years, 26 men) upon their admission to the intensive coronary care unit (ICCU). Serial ECGs were acquired following coronary revascularization and after additional 24 hours (24h). High-frequency morphology index (HFMI), quantifying the extent of ischemic patterns was computed by a custom software, and its values were compared between the serial ECG measurements. RESULTS HFMI values were significantly higher on the admission ECG as compared to the post intervention ECG (4.6 ± 2.9% vs 3.4 ± 2.3%, P < 0.05) and to the 24h ECG (4.6 ± 2.9% vs 2.8 ± 2.1%, P < 0.01). In 79% of the patients who were successfully revascularized HFMI value decreased from admission ECG to 24h ECG. CONCLUSIONS Analysis of HFQRS morphology in patients with AMI provides information about the existence and severity of myocardial ischemia. HFQRS analysis may aid in risk stratification of patients with suspected myocardial ischemia, complementarily to conventional ECG.