Purpose <p>To evaluate the safety and local efficacy of irreversible electroporation (IRE) for soft tissue lesions near or involving gastrointestinal structures.</p> Material and Methods <p>This single-center retrospective study analyzed patients treated with percutaneous IRE for lesions near or involving gastrointestinal structures from June 2018 to March 2024. Safety was assessed by complications graded according to CTCAE criteria. Efficacy, a secondary outcome, was evaluated based on tumor response and local progression-free survival (LPFS) using mRECIST and PERCIST criteria. Additional secondary outcomes included length of hospital stay.</p> Results <p>Twenty-five patients underwent IRE for 30 lesions near the stomach, small bowel, colon, or rectum. Primary cancers included pancreatic (n = 1), uterine (n = 1), urothelial (n = 2), prostate (n = 2), small intestine (n = 3), renal cell (n = 4) and colorectal (n = 12). Median age was 65&#xa0;years, mean lesion size 2.4&#xa0;cm, and technical success 100%. Complications occurred in 34.8% (all grade 1), with no gastrointestinal perforations. Median hospital stay was 1 night. Median follow-up was 25.3&#xa0;months; LPFS was 24.4&#xa0;months, with 1- and 2&#xa0;year rates of 62.0% and 54.3%. In the colorectal cancer subgroup, LPFS was 23.8&#xa0;months, with 1- and 2&#xa0;year rates of 58.7% and 47.0%, and median OS 56.1&#xa0;months (1&#xa0;year: 100%, 2&#xa0;year: 87.5%).</p> Conclusion <p>IRE is found to be safe and an effective local treatment for soft tissue metastases near the gastrointestinal tract, offering promising control with minimal complications in challenging anatomical locations.</p> <p><i>Level of Evidence</i> 4 (retrospective study without a control group)</p> Graphical Abstract <p></p>