This single-blind, placebo-controlled study evaluated long-term therapy with cibenzoline in 19 patients with chronic ventricular arrhythmias. Antiarrhythmic efficacy, defined as greater than or equal to 75% reduction in single premature ventricular complexes (PVCs), greater than or equal to 90% reduction in paired PVCs, and total abolition of ventricular tachycardia (VT), was established after dose titration in 14 of 19 (74%) patients. Mean frequency of single PVCs was reduced by 65%, mean paired PVC frequency was reduced by 68%, and mean VT event frequency was reduced by 82%. Antiarrhythmic efficacy was maintained during long-term therapy in five of the 14 (36%) short-term responders. Of the nine patients who discontinued cibenzoline during long-term follow-up, five had a loss of arrhythmia control, three failed to redevelop arrhythmias during placebo reintroduction, and one developed an adverse reaction. Three patients (16%) experienced a proarrhythmic effect. Echocardiographic evaluation did not reveal any deleterious effect of cibenzoline on left ventricular function in the group as a whole. In six patients with preexisting left ventricular dysfunction, left ventricular ejection fraction and fractional shortening improved significantly (P less than .05) during cibenzoline therapy. Adverse effects occurred in seven patients (37%) but necessitated drug discontinuation in only one patient (5%). Cibenzoline provides effective short-term therapy for patients with chronic ventricular arrhythmias. Long-term therapy must be assessed periodically to ensure continued efficacy. Drug-related adverse effects occur infrequently. Cibenzoline can be used safely in patients with compensated left ventricular dysfunction.