Diprafenone is a new antiarrhythmic agent with a dominant local anesthetic action and additional beta-sympathicolytic activity. In a randomized study, we analyzed the antiarrhythmic efficacy and tolerance of diprafenone (450-600 mg/day) in comparison to that of propafenone (450-500 mg/day) in ten patients with frequent and complex ventricular premature beats. After an initial control period, all patients received either diprafenone 450 mg/day or propafenone 450 mg/day for 5 days. In the case of a drug response (VPB suppression greater than 84%, suppression of ventricular pairs greater than 90%, suppression of ventricular tachycardia greater than 100%), after a wash-out period of 7 days patients were treated with the second antiarrhythmic medication for 5 days. In the case of nonresponsiveness, the dose of diprafenone and propafenone was increased to 600 mg/day and treatment continued for a second 5-day period. During the control period and at every drug administration, 24-h-Holter monitoring and ECG were performed, and plasma concentration and side effects were checked. After individual dose titration, 7/10 cases were effectively treated with diprafenone (mean dose: 471 mg; mean VPB suppression: 92%) and 5/10 cases with propafenone (mean dose: 540 mg; mean VPB suppression: 80%). Altogether four patients reported side effects, mainly gastrointestinal, which limited therapy in one patient in each group. Compared to propafenone, diprafenone had a strong effect on AV-nodal and ventricular conduction intervals; however, in no patient was therapy limited by these changes. Thus, also in comparison to propafenone, diprafenone is effective in the treatment of ventricular arrhythmias.