OBJECTIVE: Few data exist to guide antiarrhythmic drug therapy for sustained ventricular tachycardia/ventricular fibrillation after acute myocardial infarction. The objective of this analysis was to describe the survival of patients with sustained ventricular tachycardia/ventricular fibrillation after myocardial infarction according to antiarrhythmic drug treatment. DESIGN AND SETTING: We conducted a retrospective analysis of ST-segment elevation myocardial infarction patients with sustained ventricular tachycardia/ventricular fibrillation in Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO) IIB and GUSTO III and compared all-cause death in patients receiving amiodarone, lidocaine, or no antiarrhythmic. We used Cox proportional-hazards modeling and inverse weighted estimators to adjust for baseline characteristics, β-blocker use, and propensity to receive antiarrhythmics. Due to nonproportional hazards for death in early follow-up (0-3 hrs after sustained ventricular tachycardia/ventricular fibrillation) compared with later follow-up (>3 hrs), we analyzed all-cause mortality using time-specific hazards. PATIENTS AND INTERVENTIONS: Among 19,190 acute myocardial infarction patients, 1,126 (5.9%) developed sustained ventricular tachycardia/ventricular fibrillation and met the inclusion criteria. Patients received lidocaine (n = 664, 59.0%), amiodarone (n = 50, 4.4%), both (n = 110, 9.8%), or no antiarrhythmic (n = 302, 26.8%). RESULTS: In the first 3 hrs after ventricular tachycardia/ventricular fibrillation, amiodarone (adjusted hazard ratio 0.39, 95% confidence interval 0.21-0.71) and lidocaine (adjusted hazard ratio 0.72, 95% confidence interval 0.53-0.96) were associated with a lower hazard of death-likely evidence of survivor bias. Among patients who survived 3 hrs, amiodarone was associated with increased mortality at 30 days (adjusted hazard ratio 1.71, 95% confidence interval 1.02-2.86) and 6 months (adjusted hazard ratio 1.96, 95% confidence interval 1.21-3.16), but lidocaine was not at 30 days (adjusted hazard ratio 1.19, 95% confidence interval 0.77-1.82) or 6 months (adjusted hazard ratio 1.10, 95% confidence interval 0.73-1.66). CONCLUSION: Among patients with acute myocardial infarction complicated by sustained ventricular tachycardia/ventricular fibrillation who survive 3 hrs, amiodarone, but not lidocaine, is associated with an increased risk of death, reinforcing the need for randomized trials in this population.