Irreversible electroporation (IRE) is a new nonthermal tumor ablation modality that induces apoptosis in the treated tissue without affecting collagen. Its use is particularly indicated for tumors involving major structures, such as encompassed or infiltrated vessels and/or ducts, which need to be preserved and hinder or preclude surgical resection. We report a 66-year-old male patient with locally advanced pancreatic adenocarcinoma, treated with IRE.Two cycles of neoadjuvant chemotherapy with nab-paclitaxel and gemcitabine were administered. After these 2 cycles, IRE ablation was performed with a percutaneous transgastric access under general anesthesia. Later, 4 additional chemotherapy cycles were administrated. At 48 hours of electroporation, blood tests were normal. On day 5, a computed tomography (CT) scan showed portal vein and celiac artery were normal in appearance. Three months later, a positron emission tomography (PET) scan showed disappearance of abnormal uptake in the pancreas and other sites. A 12-month follow-up the patient is disease free.IRE opens a new way to treat tumors with involvement or proximity of neighboring structures. This procedure is more costly than other techniques and is not free of complications. The percutaneous transgastric access is feasible and without serious complications. In our case, complications were resolved and the patient presented a good short/medium-term outcome.