OBJECTIVES: The purpose of this study was to determine the mechanisms of sudden death (SD) in patients with ventricular tachyarrhythmias (ventricular tachycardia/ventricular fibrillation [VT/VF]) treated with an implantable cardioverter defibrillator (ICD). BACKGROUND: Despite ICD therapy, some patients with VT/VF still die suddenly. Optimal ICD use requires determination of the mechanisms of these residual SDs. METHODS: We reviewed 320 patient deaths during trials of Medtronic transvenous ICD systems (Medtronic Inc., Minneapolis, Minnesota). Sudden deaths were further categorized according to mechanism. Post-shock electromechanical dissociation (EMD) describes a scenario where VT/VT was appropriately detected and treated by an ICD shock that restored a physiologic rhythm, but death still occurred immediately by EMD. RESULTS: A mode of death could be ascribed for 317 patients - 90 (28%) were sudden, 156 (49%) were nonsudden cardiac, and 71 (22%) were noncardiac. A mechanism of SD was proposed for 68 patients - 20 (29%) had post-shock EMD, 17 (25%) had VT/VT uncorrected by shocks, 11 (16%) had primary electromechanical dissociation, 9 (13%) had incessant VT/VT, 5 (7%) had VT/VT after their ICD was deactivated or removed, and 6 (9%) had single instances of various other terminal events. Only New York Heart Association functional class independently predicted SD by post-shock EMD. C0NCLUSIONS: The most common mechanism of SD in patients with an ICD is VT/VT treated with an appropriate shock followed by EMD. As this mechanism accounted for 29% of the SDs to which a cause could be ascribed, this mechanism of SD warrants further investigation.