Background Irreversible electroporation (IRE) for treatment of locally advanced pancreatic tumors is garnering increasing attention. This study was conducted to determine perioperative morbidity and mortality for locally advanced pancreatic cancer. Methods Prospective data of 50 consecutive patients receiving IRE for T4 lesions at a single tertiary center were analyzed. The primary end point was Clavien–Dindo complications at 90 days, and the secondary outcomes were survival and recurrence. Results A total of 50 patients underwent 53 IRE procedures for primary treatment ( n  = 29) or margin extension ( n  = 24), and 47 patients had adenocarcinoma. Six patients died within 90 days after the procedure (5 in the primary control group). Mortality occurred a median of 26 days (range, 8–42 days) after the procedure. Five patients in both the margin-extension and primary control groups experienced grade 3 or 4 morbidity ( p  = 0.739). The incidences of grades 3 to 5 complications did not differ significantly based on the adjustable parameters of IRE, tumor size, or primary treatment versus margin extension. After a median follow-up period of 8.69 months interquartile range (IQR), 0.26–16.26 months, the median overall survival period for the primary control group was 7.71 months 95 % confidence interval (CI), 6.03–12.0 months) and was not reached in the margin-extension group ( p  = 0.01, log-rank). Conclusions At the authors’ center, the mortality rate after IRE was higher than reported in other series, with the majority occurring in the primary control group. Major morbidity trended around upper gastrointestinal bleeding, visceral ulcerations/perforations, and portal vein thromboses. This favors further investigation of the safety and efficacy of IRE.