The Electrophysiologic Study versus Electrocardiographic Monitoring (ESVEM) trial had 2 objectives. The first was to determine the accuracy of noninvasive versus invasive means of predicting the efficacy of drug treatment for ventricular tachycardia/ventricular fibrillation (VT/VF). A second objective was to determine the relative efficacies of 7 antiarrhythmic drugs used in the treatment of ventricular tachyarrhythmias. ESVEM was the first opportunity to compare prospectively the efficacy, safety, and tolerability of a variety of antiarrhythmic drugs in the same patient population. No significant difference was observed between suppression of spontaneous ventricular arrhythmias on Holter monitoring and suppression of inducible ventricular arrhythmias by electrophysiologic study (EPS) in terms of the ability to predict the success of drug therapy. There was also no difference in predictive accuracy if patients in the electrophysiologic limb showed suppression by Holter monitoring in addition to suppression by EPS. Sotalol was more effective than the other 6 antiarrhythmic drugs, all class I agents, in preventing death and recurrence of arrhythmia. Efficacy compared with placebo, however, was not evaluated. In the EPS limb, sotalol was also statistically more likely to achieve an efficacy prediction than any of the sodium channel blocking drugs. Amiodarone was not used in ESVEM. It has been suggested that these conclusions, which differ from those of other, less controlled, invasive and noninvasive studies, might be because of the particular efficacy criteria used in the ESVEM protocol. Retrospective analyses of the ESVEM data were performed using more rigid efficacy criteria than were used in the original ESVEM analysis: a greater degree of ectopy suppression was required for Holter monitoring, and more stringent efficacy definitions were required in the stimulation protocol of the EPS limb. Results from the retrospective analyses and other studies support the initial ESVEM conclusions. In patients with both spontaneous and inducible sustained ventricular tachyarrhythmias as well as frequent spontaneous premature ventricular contractions, therapy with sotalol (guided by either Holter monitoring or EPS) is a reasonable initial strategy because of its superior initial long-term efficacy and better acute and long-term tolerability compared with sodium channel blocking drugs.