Toxic megacolon is a gastrointestinal emergency requiring prompt management to avoid fatal outcome. Although a majority of patients respond to conservative treatment, those not responding have been treated with intravenous cyclosporine or emergency surgery. Infliximab has been tried in patients with severe steroid-refractory ulcerative colitis. We report the successful use of this drug in the management of toxic megacolon in a 48-year-old woman not responding to the routine measures and who refused surgery.