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What’s known on the subject? and What does the study add?IRE has been used in liver and prostate models before, confirming appropriate cell death with sharp margins of ablation. The current study confirms that this technology may also provide an effective treatment in the kidney, which provides a unique environment due to electrolyte differences, renal blood flow, and collecting system anatomy. The advantage of IRE may be that its athermal nature limits common problems with percutaneous ablation, including heat sink and destruction of the urothelium.•To evaluate the effects of irreversible electroporation (IRE) on renal parenchyma and the renal collecting system in a porcine model.•Eight female Yorkshire pigs underwent a series of laparoscopic ablations using either monopolar or bipolar IRE (Angiodynamics, Queensbury, NY, USA).•The pigs were killed between 10 min and 14 days after IRE, and the kidneys were harvested for gross and histological analysis, including NADH staining for cellular viability.•In all, 24 ablations were performed and all the pigs survived without complications.•Initial gross lesions were diffusely haemorrhagic, decreasing progressively in size (30–40%) to small white scars over the 14-day period.•Immediately after IRE, ablated tissue was characterized by diffuse tubular desquamation, eosinophilia, and nuclear pyknosis, with absence of cellular viability by NADH.•At 7 days after IRE, there was diffuse cellular necrosis with early peripheral granulation changes, and by 14 days there was marked tissue granulation, chronic inflammation, and dystrophic calcification with early fibrosis and cellular contraction.•Initial patchy urothelial injury and ulceration showed signs of repair and viability by 14 days after IRE.•Renal IRE in the porcine kidney leads to predictable histological changes characteristic of cellular death within 1 h of ablation, with relative urothelial sparing.•Further animal studies are warranted to determine safety and efficacy of this novel ablation technology.