Electrode polarity has been reported to be one of the factors that affect defibrillation efficacy. We studied the influence of polarity on defibrillation efficacy when monophasic and biphasic waveforms were used with an endocardial lead system. In six anesthetized pigs, defibrillation catheters were placed in the right ventricular (RV) apex and at the junction of the superior vena cava (SVC) and right atrium. Monophasic shocks were 6 ms in duration, while for biphasic shocks the first phase was 6 ms and the second was 4 ms in duration. Four electrode configurations were tested: R:S, M (the RV electrode, cathode; the SVC electrode, anode, with a monophasic shock); S:R, M; R:S, B (the RV electrode, first phase cathode; the SVC electrode, first phase anode, with a biphasic shock); S:R, B. Defibrillation probability of success curves were determined using an up/down protocol requiring 15 shocks for each configuration. For monophasic shocks, total delivered energy at the 50% probability of success point was significantly lower when the RV electrode was an anode than when it was a cathode (R:S, M: 24.4 ± 7.4 J [mean ± SD] vs S:R, M: 16.4 ± 5.5 J; P < 0.05). For biphasic shocks, total energy was not affected by polarity reversal of the electrodes (R:S, B: 8.7 ± 1.4 J vs S:R, B: 8.4 ± 2.5 J; P = NS). The endocardial electrode configuration with the RV electrode as an anode requires less energy for defibrillation with a monophasic but not a biphasic waveform.