Background: Colonic pseudo-obstruction is a poorly understood syndrome, described by Ogilvie,1 and characterized by signs of large-bowel obstruction, without a mechanical cause. An imbalance in the autonomic nerve supply to the colon has been suggested as the pathophysiology. Recently, promising results with pharmacologic manipulation with neostigmine have been described. Study Design: A prospective study was undertaken with 11 consecutive patients with clinical and radiologic signs of colonic pseudo-obstruction, in one general hospital, over a 1-year period. Patients were treated primarily with 2.5 mg of neostigmine in 100 mL of saline for 1 hour, under cardiac monitoring. Results were assessed by the clinical and radiologic responses. Results: Rapid and effective spontaneous decompression of the colon was achieved in 8 patients after a single dose of neostigmine, within a mean of 90 minutes from the beginning of treatment. In another two patients decompression occurred only after a second dose was administered 3 hours after the first dose. In one patient, no changes were observed and colonoscopic decompression was performed. No significant bradycardia was observed in any of the patients. Conclusions: Neostigmine is a simple, safe, and effective therapy for treatment of colonic pseudo-obstruction.