We aimed to evaluate the effect of defibrillator component positioning on high-voltage impedance. In two human specimens with BMI 19.1 kg/m 2 and 31.4 kg/m 2, shocks were administered with a subcutaneous implantable cardioverter-defibrillator (S-ICD) and an automated external defibrillator placed in various positions. High-voltage impedance increased with more fat tissue between the defibrillator components, or with air in the subcutaneous pocket of the S-ICD. High-voltage impedance was lowest when defibrillator components were placed anteriorly, but due to adjacent positioning, the electrical current will not be transmitted through the myocardium and effective defibrillation is unlikely. In conclusion, positioning of defibrillator components greatly affects high-voltage impedance, but the course of the current should always be considered.