Background: Intravenous neostigmine is a well-established treatment for acute colonic pseudo-obstruction (ACPO). Its use is hampered by the perceived requirement for continuous cardiac monitoring, and patients are often transferred to high-dependency units for close observation during treatment. Subcutaneous neostigmine has the potential to minimize adverse cardiovascular effects while maintaining efficacy. This study aims to assess the safety of subcutaneous neostigmine on ward inpatients with ACPO monitored with standard nursing care. Methods: This is a retrospective case series of 30 patients with ACPO who were treated with subcutaneous neostigmine between August 2008 and October 2012. Data were collected prospectively. All patients were diagnosed using clinical examination and radiology and were assessed for contraindications to neostigmine. Patients were treated on regular wards and monitored with standard nursing observations. The main outcomes were time to flatus and bowels working and complications. Results: No serious complications such as clinically evident bradycardia were encountered. Ninety-three percent of patients had clinically successful resolution of ACPO. Two patients (7%) developed caecal tenderness and proceeded to colonoscopic decompression, which was successful in both instances. Conclusions: Subcutaneous neostigmine appears to be safe for the treatment of ACPO. No clinically evident serious adverse events occurred, meaning continuous cardiac monitoring as a routine may not be necessary. In our cohort, we achieved similar success rates compared with reported rates using intravenous neostigmine.