Purpose To develop and validate a perfused organ model for characterizing ablations for irreversible electroporation (IRE)–based therapies. Materials and Methods Eight excised porcine livers were mechanically perfused with a modified phosphate-buffered saline solution to maintain viability during IRE ablation. IRE pulses were delivered using 2 monopolar electrodes over a range of parameters, including voltage (1,875–3,000 V), pulse length (70–100 µsec), number of pulses (50–600), electrode exposure (1.0–2.0 cm), and electrode spacing (1.5–2.0 cm). Organs were dissected, and treatment zones were stained with triphenyl tetrazolium chloride to demonstrate viability and highlight the area of ablation. Results were compared with 17 in vivo ablations performed in canine livers and 35 previously published ablations performed in porcine livers. Results Ablation dimensions in the perfused model correlated well with corresponding in vivo ablations (R2 = 0.9098) with a 95% confidence interval of < 2.2 mm. Additionally, the validated perfused model showed that the IRE ablation zone grew logarithmically with increasing pulse numbers, showing small difference in ablation size over 200–600 pulses (3.2 mm ± 3.8 width and 5.2 mm ± 3.9 height). Conclusions The perfused organ model provides an alternative to animal trials for investigation of IRE treatments. It may have an important role in the future development of new devices, algorithms, and techniques for this therapy.