The Cardiac Arrest in Seattle: Conventional Versus Amiodarone Drug Evaluation (CASCADE) study evaluated antiarrhythmic drug treatment of survivors of out-of-hospital ventricular fibrillation (VF) not associated with a Q-wave myocardial infarction who were at especially high risk of recurrence of VF. Therapy was randomized to empiric treatment with amiodarone versus treatment with other antiarrhythmic drugs guided by electrophysiologic testing, Holter recording, or both (conventional therapy). The primary end points of the study were cardiac mortality, resuscitated cardiac arrest due to documented VF, or complete syncope followed by a shock from an implanted automatic defibrillator. Two hundred twenty-eight patients were enrolled in the study, and baseline characteristics were similar in the patients treated with amiodarone and with conventional therapy. Two hundred two patients (89%) were men with an average age of 62 years. Coronary artery disease was the most common underlying condition (188 of 228, 82%), and in coronary patients, 153 of 188 (81%) had experienced a prior myocardial infarction before the index VF event. Mean left ventricular ejection fraction was 0.35, and 102 patients (45%) had a prior history of congestive heart failure. Survival free of cardiac death, resuscitated VF, or syncopal defibrillator shock for the entire population was 75% at 2 years (amiodarone, 82%; conventional, 69%), 59% at 4 years (amiodarone, 66%; conventional, 52%), and 46% at 6 years (amiodarone, 53%; conventional, 40%); p = 0.007. The survival free of cardiac death and sustained ventricular arrhythmias was 65% at 2 years (amiodarone, 78%; conventional, 52%), 43% at 4 years (amiodarone, 52%; conventional, 36%), and 30% at 6 years (amiodarone, 41%; conventional, 20%); p < 0.001.