Background-This study investigates the hypothesis that morphologic analysis of intracardiac electrograms provides a sensitive approach to detect acute myocardial infarction or myocardial infarction-induced arrhythmia susceptibility. Large proportions of irreversible myocardial injury and fatal ventricular tachyarrhythmias occur in the first hour after coronary occlusion; therefore, early detection of acute myocardial infarction may improve clinical outcomes. Methods and Results-We developed a method that uses the wavelet transform to delineate electrocardiographic signals, and we have devised an index to quantify the ischemia-induced changes in these signals. We recorded body-surface and intracardiac electrograms at baseline and following myocardial infarction in 24 swine. Statistically significant ischemia-induced changes after the initiation of occlusion compared with baseline were detectable within 30 seconds in intracardiac left ventricle (P<0.0016) and right ventricle-coronary sinus (P<0.0011) leads, 60 seconds in coronary sinus leads (P<0.0002), 90 seconds in right ventricle leads (P<0.0020), and 360 seconds in body-surface electrocardiographic signals (P<0.0022). Intracardiac leads exhibited a higher probability of detecting ischemia-induced changes than body-surface leads (P<0.0381), and the right ventricle-coronary sinus configuration provided the highest sensitivity (96%). The 24-hour ECG recordings showed that the ischemic index is statistically significantly increased compared with baseline in lead I, aVR, and all precordial leads (P<0.0388). Finally, we showed that the ischemic index in intracardiac electrograms is significantly increased preceding ventricular tachyarrhythmic events (P<0.0360). Conclusions-We present a novel method that is capable of detecting ischemia-induced changes in intracardiac electrograms as early as 30 seconds following myocardial infarction or as early as 12 minutes preceding tachyarrhythmic events.