A comparative, fixed-dose, parallel, randomized, blinded trial to define the efficacy and safety of a new once-a-day quinidine preparation, Quiniday, at 1200 mg per day, was compared to quinidine sulfate (as Quinora, 300 mg four times daily, and Quinidex Extentabs, 600 mg twice daily) and to quinidine gluconate (as Quinaglute Dura-Tabs, 648 mg twice daily). After placebo washout from all prior antiarrhythmic agents, 76 patients with at least 30 ventricular premature complexes (VPCs)/hr on 48-hour ambulatory monitoring were randomized to 3 weeks of treatment with one of the four study drugs. There was no difference in the etiologic, demographic, New York Heart Association therapeutic classification, or ventricular arrhythmia frequency at baseline between the patients randomized to the four groups. There was no statistically significant difference between the percent efficacy for VPC reduction on any drug compared to baseline or in the percent efficacy of reduction in beats of ventricular tachycardia. There was no difference between the four agents in terms of types of side effects noted nor in their overall prevalence or need for premature discontinuation of therapy. This study demonstrated that a variety of quinidine preparations exist that do not differ in terms of their efficacy or safety, but that a long-acting, once-a-day preparation (Quiniday) was as effective and safe as other forms of quinidine despite its once-a-day dosing schedule. More compliant dosing regimens with effective well-known antiarrhythmic agents are important in the treatment of patients with potentially lethal ventricular arrhythmias, in the hope that sudden cardiac death can be prevented.