The effectiveness of oral propafenone in treating ventricular premature complexes (VPCs) was assessed with a single-blind dose-ranging trial followed by a double-blind, randomized, crossover comparison of propafenone and placebo. Patients subsequently were treated with propafenone for up to 24 months. During dose ranging, the average of individual percent suppressions was 83 % at the largest dose (300 mg/8 hours). During the double-blind trial, the effectiveness of propafenone was confirmed, with 7 of 12 patients achieving ≥80 % reduction in VPCs (p <0.05 versus double-blind placebo study). Propafenone was also effective in controlling couplets and nonsustained ventricular tachycardia. Seven patients were treated with propafenone for 24 months, during which effectiveness continued, with mean suppression ranging from 67 to 79 % (p <0.05 versus initial single-blind placebo). Propafenone prolonged PR and QRS intervals by 16 and 18 %, respectively; these prolongations continued during long-term therapy. Propafenone increased serum digoxin levels in 5 of 5 patients (mean increase 83 %). Cardiovascular side effects included congestive heart failure (1 patient) and conduction abnormalities (3 patients). Thus, propafenone was effective in the treatment of total and repetitive VPCs. Side effects were few, but congestive heart failure, conduction disturbances and increases in serum digoxin were observed.