Background Single-lead ECG devices may allow detection and diagnosis of cardiac rhythms. However, data on their accuracy for detecting cardiac arrhythmias beyond atrial fibrillation are limited. Objectives To determine the accuracy of the AliveCor KardiaMobile (AC; AliveCor Inc, Mountain View, CA) for the diagnosis of arrhythmias against gold standard cardiac electrophysiology study (EPS). Methods Patients undergoing clinically indicated EPS underwent simultaneous rhythms recording with an infraclavicular-placed AC, standard 12-lead ECG and EP catheters for intracardiac electrograms. Rhythms recorded during EPS were classified based on electrogram, 12-lead ECG and clinical findings. Blinded reviewers provided differential diagnoses for the single-lead AC tracings; a separate reviewer compared diagnoses made between the AC tracings and EPS findings. Results From 49 patients, 843 cardiac rhythms were captured during 502 AC recordings. Analysis of tracings containing sinus rhythm (n=273) returned overall accuracy of 92%, with sensitivity and specificity values of 93% and 92%, respectively. Accuracy for tracings per rhythm were atrial fibrillation 91% (n=51); supraventricular tachycardia accuracy was 89% (n=191), ventricular tachycardia 91% (n=198), ventricular fibrillation 98% (n=11), asystole 100% (n=5). Accuracy for supraventricular ectopy was 93% (n=28) and premature ventricular complexes was 91% (n=86). Overall accuracy was 94% for uninterrupted rhythms and 93% in tracings from patients with baseline bundle branch block. Conclusions When compared against the gold standard EPS diagnosis, interpretation of arrhythmias recorded by an AliveCor single-lead ECG device had reasonable diagnostic accuracy.