The electrophysiologic and electrocardiographic effects, efficacy and safety of encainide were evaluated in 48 patients with coronary artery disease undergoing programmed stimulation for ventricular tachyarrhythmias. The study group included 41 men and 7 women, aged 64 ± 8 years (mean ± standard deviation), who had presented with nonsustained ventricular tachycardia (VT) (4 patients), sustained VT (32), ventricular fibrillation (8) or unexplained syncope (4). The left ventricular ejection fraction averaged 34 ± 13%. The arrhythmias induced at the baseline, drug-free electrophysiologic study included nonsustained VT in 8 patients, sustained VT in 35 and ventricular fibrillation in 5. All patients had failed ≥1 class IA and a combination of class IA and IB agents (mean 2.2 ± 1.1 drugs) before encainide. Oral encainide was given in a mean daily dose of 80 ± 11 mg for ≥3 days before repeat programmed stimulation. Encainide was discontinued before follow-up electrophysiologic testing in 5 patients due to spontaneous development of new sustained VT. Of the 43 patients undergoing electropharmacologic testing with encainide, 5 had no inducible arrhythmia. In 9 patients VT was inducible by fewer extrastimuli, in 2 patients a previously stable VT required cardioversion, whereas in 28 patients VT remained inducible by the same number of or more extrastimuli. Thus, encainide prevented the induction of VT or ventricular fibrillation in 5 of 48 patients (10%), while it had a possible proarrhythmic effect in 15 patients (31%). Of the 5 patients without inducible VT administered long-term encainide therapy, 1 returned within 4 weeks of hospital discharge with VT recurrence. Encainide has limited efficacy (10%) for prevention of ventricular arrhythmia induction by programmed stimulation, a high incidence of possible proarrhythmia (31%) and a late failure rate of 20% (1 of 5) despite noninducibility at electrophysiologic testing.