Objective: The objective of this study was to test the hypothesis that on the epicardium of the in vivo human heart, ventricular fibrillation (VF) consists of chaotic small wavefronts that constantly change paths. Background: Despite the significance of VF to cardiovascular mortality, little is known about the wavefronts that constitute VF in humans. Methods: In 9 patients undergoing cardiac surgery, a single VF episode was induced by rapid pacing immediately after institution of cardiopulmonary bypass while recordings were made from 504 electrodes spaced 2 mm apart in a 20 cm2 plaque held against the anterior left ventricle epicardium. A total of 26 segments of VF, each 2 s long, were analyzed. A computer algorithm identified individual wavefronts and classified them into groups that followed similar activation sequences. Results: The mean activation rate was 5.8 ± 1.8 (mean ± SD) cycles/s. The wavefronts during each epoch were grouped into 9.4 ± 7.1 different activation pathways, and 8.3 ± 2.3 wavefronts followed each pathway. Individual wavefronts spread to activate an area of 5.1 ± 3.0 cm2 in the mapped region. The majority of the wavefronts propagated into the mapped region and/or propagated out of the mapped region into adjacent tissue, suggesting that the wavefronts were larger than 5.1 cm2. Reentry was identified in only 16 of the 26 (62%) 2-s segments, always completed <2 cycles, and lasted for 9.5 ± 6.6% of these 16 epochs, which is 5.8% of the total duration of all the segments analyzed. Conclusion: VF wavefronts on the human epicardium are usually large, repeatedly follow distinct pathways, and only occasionally reenter. If these results for the left ventricular epicardium are representative of those for the entire ventricular mass, they do not support the hypothesis that human VF consists of small, constantly changing wavefronts, but rather suggest that there is significant organization of human VF. © 2004 Heart Rhythm Society. All rights reserved.