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<h3>Introduction</h3> Malignant bowel obstruction (MBO) is a common complication in patients with advanced intra-abdominal cancer. Obstruction may be mechanical or functional, the latter arising secondary to impaired gastrointestinal motility. Functional MBO presents a significant management challenge in palliative care, particularly when standard management options fail. Neostigmine, a cholinesterase inhibitor with prokinetic action, is rarely reported in functional MBO but may offer an innovative approach. This report presents a novel, off-license application of neostigmine in a palliative patient with functional MBO, showcasing how coordinated multidisciplinary care can restore bowel function, resolve symptoms and improve quality of life. <h3>Methods</h3> A 62-year-old man with metastatic colorectal cancer and pre-existing stoma underwent laparotomy for presumed mechanical large bowel obstruction. No mechanical cause was identified intra-operatively. Post-operatively, bowel rest and prokinetic therapy (metoclopramide, prucalopride) failed to relieve abdominal distension and pain, and stoma output remained absent. Palliative care provided ongoing analgesic support, while gastroenterology initiated an off-license trial of intravenous neostigmine in Critical Care. The patient received four daily doses of 2.5 mg with high-dependency monitoring and multidisciplinary oversight. <h3>Results</h3> Each dose of intravenous neostigmine produced rapid stoma output. Four doses were required for sustained, spontaneous bowel function and resolution of obstructive symptoms. This enabled step-down from Critical Care and subsequent discharge home. No major physical adverse effects were observed. The patient experienced psychological distress related to the Critical Care environment and use of neostigmine, highlighting the necessity for concurrent psychosocial support alongside physical symptom management. <h3>Conclusions</h3> This case demonstrates the potential role of neostigmine in functional MBO which is unresponsive to standard therapies and causing symptoms that significantly impact quality of life. Its use requires close monitoring and multidisciplinary collaboration. While neostigmine can dramatically improve obstructive symptoms, clinicians must balance physiological benefit with the psychological and ethical considerations of invasive interventions in palliative patients.