OBJECTIVES: The goal of this study was to determine if the defibrillation threshold (DFT) after spontaneous ventricular fibrillation (VF) secondary to acute ischemia differs from the DFT for electrically induced VF in the absence of ischemia in anesthetized, closed-chest dogs and pigs. BACKGROUND: The efficacy of external defibrillators has been tested mainly in animals and humans using E-VF, yet external defibrillators are often used in patients to halt S-VF. METHODS: Protocol 1: biphasic truncated exponential (BTE) waveform shocks were delivered through electrodes placed in an anterior-anterior (A-A) position (left and right lateral thorax) in nine dogs. After measuring the E-VF DFT, acute ischemia was induced with an angioplasty balloon in either the left anterior descending or left circumflex coronary artery, and the S-VF DFT was determined. Protocol 2: in a group of 12 pigs, the E-VF DFT and S-VF DFT were determined for electrodes in the A-A position and in the anterior-posterior position (A-P). Protocol 3: the E-VF DFT was determined in seven pigs. Then up to three shocks 1.5× the E-VF DFT were delivered to S-VF. If defibrillation did not occur, a step-up protocol was used until defibrillation occurred. RESULTS: Protocol 1: the DFT for E-VF was 65 ± 28 J (mean ± SD) compared with 226 ± 97 J for S-VF, p < 0.05. Protocol 2: the DFT was 152 ± 58 J for E-VF and 315 ± 123 J for S-VF for A-A electrodes. The DFT was 100 ± 43 J for E-VF and 206 ± 114 J for S-VF for A-P electrodes. Protocol 3: 11/37 shocks of strength 1.5× E-VF DFT (182 ± 40 J) stopped the arrhythmia. The episodes of S-VF not halted by these shocks required energy levels of up to 400 J for defibrillation. CONCLUSIONS: External defibrillation of S-VF induced by acute ischemia requires significantly more energy than VF induced by 60-Hz current in the absence of ischemia. A safety margin >1.5× the DFT for electrically induced VF may be necessary in BTE external defibrillators to defibrillate S-VF. © 2002 by the American College of Cardiology.