The Cardiac Arrest in Seattle: Conventional Versus Amiodarone Drug Evaluation (CASCADE) study evaluated antiarrhythmic drug therapy in patients who had survived an episode of out-of-hospital ventricular fibrillation (VF) and who were thought to be at high risk for recurrence of VF. Therapy with empiric amiodarone was compared to therapy with other antiarrhythmic agents, guided by electrophysiologic testing and/or Holter recording. The study evaluated the endpoints of (1) cardiac death, (2) cardiac arrest from ventricular fibrillation with resuscitation, and (3) complete syncope followed by a shock from an automatic implanted defibrillator that restored consciousness. The study comprised 228 patients, 113 treated with amiodarone and 115 treated with conventional antiarrhythmic drug therapy. Most patients had coronary artery disease with a prior myocardial infarction, and one half of the population had a history of congestive heart failure. The mean left ventricular ejection fraction was 35%. Survival was better in patients treated with amiodarone than in patients treated with other antiarrhythmic agents. Patients treated with amiodarone were less likely to receive a shock from an implanted defibrillator, and syncope followed by a shock from a defibrillator was less common in patients treated with amiodarone. However, overall mortality was high, and side effects of therapy were common. Patients treated with amiodarone, even at the low doses used in this study, were still at risk for thyroid dysfunction (both hyperthyroidism and hypothyroidism) and for pulmonary toxicity.