Wavefront synchronization is an important aspect preceding the termination of ventricular fibrillation (VF). We designed a novel approach using multi-electrode pacing that could reduce the energy consumption of successful defibrillation by more than 100-fold. We compared the efficacy of a synchronized pacing algorithm using optical recording-guided pacing at the right ventricle and the posterior left ventricle in isolated rabbit hearts. Two modes of pacing were used in the study. The electrodes were individually controlled (independent mode, ISyncP) or fired together (simultaneous mode, SSyncP) when triggered by tissue polarization at a reference site separate from the pacing sites. The hearts were stained with voltage-sensitive dye and illuminated with laser for epifluorescence imaging during pacing. The number of phase singularities of VF propagation was used to estimate the complexity of VF. A decrease in the number of PS signified a higher degree of VF organization. We found that the pacing algorithm was more effective if the pacing was applied to the posterior left ventricle than to the right ventricle. Pacing in the posterior left ventricle resulted in a 25.3% decrease in the number of PS for ISyncP and a 31% decrease for SSyncP. Pacing in the right ventricle resulted in a 29.0% decrease for ISyncP and a 2.3% increase for SSyncP. The 5mA current reflected a 27.8% decrease for ISyncP and a 32.2% decrease for SSyncP, whereas the 10mA current reflected a 27.2% decrease for ISyncP and a 5.2% increase for SSyncP. We conclude that synchronized pacing can induce VF organization, and the efficacy is higher when pacing in the left ventricle with 5 mA.