Although effects of shock strength and waveform on cardiac vulnerability to electric shocks have been extensively documented, the contribution of ventricular anatomy to shock-induced polarization and postshock propagation and thus, to shock outcome, has never been quantified; this is caused by lack of experimental methodology capable of mapping 3-D electrical activity. The goal of this study was to use optical imaging experiments and 3-D bidomain simulations to investigate the role of structural differences between left and right ventricles in vulnerability to electric shocks in rabbit hearts. The ventricles were paced apically, and uniform-field, truncated-exponential, monophasic shocks of reversed polarity were applied over a range of coupling intervals (CIs) in experiment and model. Experiments and simulations revealed that reversing the direction of externally-applied field (RV− or LV− shocks) alters the shape of the vulnerability area (VA), the 2-D grid encompassing episodes of arrhythmia induction. For RV− shocks, VA was nearly rectangular indicating little dependence of postshock arrhythmogenesis on CI. For LV− shocks, the probability of arrhythmia induction was higher for longer than for shorter CIs. The 3-D simulations demonstrated that these effects stem from the fact that reversal of field direction results in relocation of the main postshock excitable area from LV wall (RV− shocks) to septum (LV− shocks). Furthermore, the effect of septal (but not LV) excitable area in postshock propagation was found to strongly depend on preshock state. Knowledge regarding the location of the main postshock excitable area within the 3-D ventricular volume could be important for improving defibrillation efficacy.