Repolarization alternans (RA) has been implicated in the pathogenesis of ventricular arrhythmias and sudden cardiac death. We developed a 12-lead, blue-tooth/Smart-Phone (Android) based electrocardiogram (ECG) acquisition and monitoring system (cvrPhone), and an application to estimate RA, in real-time. In in-vivo swine studies (N = 17), 12-lead ECG signals were recorded at baseline and following coronary artery occlusion. RA was estimated using the Fast Fourier Transform (FFT) method using a custom developed algorithm in JAVA. Underlying ischemia was detected using a custom developed ischemic index. RA from each lead showed a significant (p < 0.05) increase within 1 min of occlusion compared to baseline (n = 29). Following myocardial infarction, spontaneous ventricular tachycardia episodes (n = 4) were preceded by significant (p < 0.05) increase of RA prior to the onset of the tachy-arrhythmias. Similarly, the ischemic index exhibited a significant increase following myocardial infarction (p < 0.05) and preceding a tachy-arrhythmic event. In conclusion, RA can be effectively estimated using surface lead electrocardiograms by analyzing beat-to-beat variability in ECG morphology using a smartphone based platform. cvrPhone can be used to detect myocardial ischemia and arrhythmia susceptibility using a user-friendly, clinically acceptable, mobile platform.