The present trial was a placebo-controlled, randomized, parallel study comparing indecainide to procainamide. A 24-hour intravenous phase measured and compared invasive hemodynamics, followed by oral administration for assessment of arrhythmia suppression. Thirty-two patients (mean age 61 years) with asymptomatic or mildly symptomatic nonsustained ventricular tachycardia (VT) were evaluated, 15 while receiving indecainide and 17 while receiving procainamide. A total of 8 patients had serious toxicity during the intravenous phase; 6 receiving indecainide experienced increased left ventricular dysfunction or worsening arrhythmia (sustained VT, arrhythmic death) while 2 receiving procainamide developed serious hypotension. Proarrhythmia developed in 3 of 15 (20%) of the indecainide patients, but in no procainamide patient. In those tolerating indecainide, long-term suppression of ventricular premature complexes (VPCs) and of runs of VT was more consistent than with procainamide. While indecainide was a potent suppressor of spontaneous VPCs and VT, patients with significant left ventricular dysfunction could not tolerate it. The indecainide patients developing serious toxicity had a common hemodynamic profile: ejection fraction less than 25%, elevated left ventricular filling pressures, low cardiac and stroke volume index and minimal cardiac reserve. Indecainide has a poor risk-benefit ratio in patients similar to the current population, who have potentially lethal ventricular arrhythmias and severe left ventricular dysfunction.