AbstractIrreversible electroporation (IRE) has recently gained in popularity as an ablative technique, however little is known about its oncological long-term outcomes. To determine the long-time survival of animals treated with a high dose of IRE and which histological changes it induces in tumoral tissue, IRE ablation was performed in forty-six athymic-nude mice with KM12C tumors implanted in the liver by applying electric current with different voltages (2000 V/cm, 1000 V/cm). The tumors were allowed to continue to grow until the animals reached the end-point criteria. Histology was harvested and the extent of tumor necrosis was semi-quantitatively assessed. IRE treatment with the 2000 V/cm protocol significantly prolonged median mouse survival from 74.3 ± 6.9 days in the sham group to 112.5 ± 15.2 days in the 2000 V/cm group. No differences were observed between the mean survival of the 1000 V/cm and the sham group (83.2 ± 16.4 days, p = 0.62). Histology revealed 63.05% ± 23.12 of tumor necrosis in animals of the 2000 V/cm group as compared to 17.50% ± 2.50 in the 1000 V/cm group and 25.6% ± 22.1 in the Sham group (p = 0.001). IRE prolonged the survival of animals treated with the highest electric field (2000 V/cm). The animals in this group showed significantly higher rate of tumoral necrosis.