BACKGROUND: Clinical trials have shown that implantable cardioverter defibrillators (ICDs) improve survival in patients with sustained ventricular arrhythmias. OBJECTIVE: To determine the efficacy necessary to make prophylactic ICD or amiodarone therapy cost-effective in patients with myocardial infarction. DESIGN: Markov model-based cost utility analysis. DATA SOURCES: Survival, cardiac death, and inpatient costs were estimated on the basis of the Myocardial Infarction Triage and Intervention registry. Other data were derived from the literature. TARGET POPULATION: Patients with past myocardial infarction who did not have sustained ventricular arrhythmia. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTIONS: ICD or amiodarone compared with no treatment. OUTCOME MEASURES: Life-years, quality-adjusted life-years (QALYs), costs, number needed to treat, and incremental cost-effectiveness. RESULTS OF BASE-CASE ANALYSIS: Compared with no treatment, ICD use led to the greatest QALYs and the highest expenditures. Amiodarone use resulted in intermediate QALYs and costs. To obtain acceptable cost-effectiveness thresholds (</=$75,000/QALY), ICDs had to reduce arrhythmic death by 50% and amiodarone had to reduce total death by 7% in patients with depressed ejection fraction. RESULTS OF SENSITIVITY ANALYSIS: For moderate efficacies, in patients with ejection fractions less than or equal to 0.3, 0.31 to 0.4, and greater than 0.4, the cost-effectiveness of amiodarone compared with no therapy was $43,100/QALY, $66,500/QALY, and $132,500/QALY, respectively, and the cost-effectiveness of ICD compared with amiodarone was $71,800/QALY, $195,700/QALY, and $557,900/QALY, respectively. CONCLUSIONS: Use of ICD or amiodarone in patients with past myocardial infarction and severely depressed left ventricular function may provide substantial clinical benefit at an acceptable cost. These results highlight the importance of clinical trials of ICDs in patients with low ejection fractions who have had myocardial infarction.