INTRODUCTION: A failed near-threshold defibrillation shock is followed by an isoelectric window (IEW) and rapid repetitive responses that reinitiate ventricular fibrillation (VF). We hypothesized that properly timed (synchronized) postshock pacing stimuli (SyncP) may capture the recovered tissues during the repetitive responses and prevent postshock reinitiation of VF, resulting in improved defibrillation efficacy. METHODS AND RESULTS: We explored the effect of postshock SyncP on defibrillation efficacy in isolated rabbit hearts (n = 12). Optical recording-guided real-time detection and electrical stimulation (5 mA) of recovered tissues in anterior/posterior left ventricle (LV) were performed following IEW. The IEW duration was found to be 69 +/- 13 ms. With the same shock strength, successful and failed defibrillation episodes were associated with 50% and 15% of the myocardium, respectively, captured by the SyncP (P < 0.001). Electrical stimulation from the posterior LV resulted in 75% of episodes capturing myocardium, as compared with anterior LV stimulation (55%; P < 0.01) and higher successful defibrillation rate (14%, posterior vs. 3%, anterior LV). The overall success in terminating VF by postshock SyncP was approximately 10%. The causes for failed myocardium capture by postshock SyncP included lack of IEW after low-strength shock (42.9%), incorrect locations of reference site (25.7%) and pacing electrodes (17.9%), and others, such as wave breakthroughs (13.5%). CONCLUSION: Postshock SyncP was feasible and the larger the myocardium captured area, the more likely was the successful defibrillation. Postshock SyncP delivered to the posterior LV was more effective than anterior LV to terminate VF.