Background: Toxic megacolon (TM) is a potentially lethal complication of idiopathic inflammatory bowel disease or infectious colitis, characterized by total or segmental non-obstructive colonic dilatation of at least 6 cm associated with systemic toxicity. Methods: Overall, 15 patients had surgery for TM at our institutions over a 10-year period (1993–2003). In contrast to other studies that used medical therapy as the first-line treatment for TM, in our experience all patients underwent surgery as soon as possible after diagnosis of TM (early surgery). Results: 14 patients underwent subtotal colectomy with terminal ileostomy, while for 1 patient the surgical procedure consisted only in a decompressive cecostomy. Two major complications occurred consisting of 2 cases of multiple organ failure leading to death. No other major complications or deaths were reported. The overall mortality rate was therefore 13% (0% in patients <65 years). Conclusion: This study shows that early surgery has the potential to represent a valid therapeutic strategy for patients with TM resulting in a small number of TM-related complications and deaths. Elderly patients seem to have a high risk of multiple organ dysfunction syndrome and post-surgical death.