Recent studies have found that when multiple pulses of energy are used for defibrillation with implantable electrodes, the spacing between these pulses is better determined as a percentage of the fibrillation cycle length (CL), rather than as a fixed function of time. Here, this concept is further tested in the transthoracic defibrillation of calves, which are approximately the size of heavy humans. Eleven 90–110 kg calves (101 ± 6 kg) were used in evaluating the effectiveness in achieving transthoracic ventricular defibrillation of ten double pulse waveforms (two 50 A 4-ms rectangular monopulses) having leading edge-to-edge spacings of 4 ms (a 50 A 8-ms rectangular monopulse) and 50, 60, 70, 80, 90, 100, 110, 120, 130 percent fibrillation CL, respectively. In each of these waveforms, the total time when 50 A current was flowing (on time) was 8 ms. Our results show an unequivocal adverse interaction between the pulses, when the spacing is around 60%–70% fibrillation CL; but that the two pulses combined to defibrillate as effectively as a single 8-ms pulse when the spacing is around 110%–130% fibrillation CL. Electrocardiographic analysis suggests that the adverse interaction is due to a refibrillation phenomenon. This study confirms that double pulses can interact and have a negative effect on defibrillation efficacy. Our data suggests that the mechanism of this interaction involves the second pulse reinitiating fibrillation when the pulse separation is in a critical range of values. Our results are also compatible with the hypothesis that the spacing of multiple pulses is better determined as a percentage of the fibrillation CL than as absolute time, although more study is necessary to fully test this hypothesis.