Class I antiarrhythmic drugs may increase the incidence of cardiac death, and controlled treatment is required in patients with severe ventricular arrhythmias. Electrophysiologically guided antiarrhythmic therapy remains an important method to manage patients with sustained ventricular tachycardia (VT). The purpose of the study was to evaluate the correlations between baseline heart rate variability in ambulatory electrocardiographic recordings of patients with sustained ventricular tachycardia and the response to hydroquinidine on VT inducibility, and to look for the changes in heart rate variability during hydroquinidine treatment. Thirty-five patients with spontaneous and inducible sustained VT were studied. Programmed ventricular stimulation and time and frequency domain analysis of heart rate variability were studied in the control state and 9–12 days after treatment with 300–600 mg of hydroquinidine. In 11 patients (group I), hydroquinidine prevented VT induction. In 24 patients (group II), sustained VT remained inducible during treatment with hydroquinidine. In the control state, heart rate variability was similar in both groups. During treatment with hydroquinidine, heart rate variability tended to decrease in groups I and II, but the changes were significant only in group II: the coefficient of variance (CV) decreased from 13 ± 4% to 10% ± 3% (p > 0.01) and low frequency/high frequency amplitude ratio decreased from 4.6 ± 3.3 to 2.87 ± 2.42 (p > 0.05). In conclusion, baseline heart rate variability does not differentiate the responders and nonresponders to hydroquinidine. Hydroquinidine decreases heart rate variability in all patients, but principally in those with still inducible VT.