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Introduction: the standard treatment for patients with locally advanced unresectable pancreatic cancer (LAUPC) is chemotherapy with the median overall survival (OS) 12-15 months. Superior mesenteric artery (SMA) resection for LAUPC patients is a rare and unsafe procedure with poor long-term results. Considering the absence of metastasis, local therapy could be added to the systemic therapy. Objective: to improve the results of treatment for LAUPC patients, using the irreversible electroporation (IEP). Materials and Methods: between Feb/2015 and Feb/2017 at Blokhin National Medical Research Center of Oncology, 7 patients were treated with IEP for LAUPC. Perioperative treatment was routinely used; one patient could not receive both an adequate pre- and postoperative therapy due to side effects. The median duration of preoperative therapy was 4 months (2-12). Two patients showed partial response and four developed stabilization after the induction chemotherapy. The median tumor size was 40mm (32-65) before any treatment and 37mm (22-65) before IEP. Results: two patients had pancreonecrosis after IEP (28.6%). One died on the 21st day. Autopsy showed no evidence of tumor in the site of IEP. The median follow up was 25 months after IEP and 30 months after the start of treatment. The median progression free survival (PFS) after IEP was 7 months, the median OS was not reached. The median PFS after the start of treatment was 14 months, the median OS was not reached. 3-year PFS and 3-year OS after start of treatment were 14.3% and 57.1%, respectively. Conclusion: IEP is the effective local destruction method for the LAUPC patients. Additional therapy is recommended. IEP of residual tumor with palliative resection of the pancreas can be an effective and safe alternative to the Whipple procedure in combination with arterial resection for LAUPC patients and SMA involvement.