Objectives: To present, to our knowledge, the largest experience with colectomy for fulminant Clostridium difficile colitis and to propose factors significant in predicting mortality. Design: Retrospective medical record review. Setting: University teaching hospital. Patients: Seventy-three patients undergoing colectomy between 1994 and 2005 for C difficile-associated pseudomembranous colitis. Main Outcome Measures: Preoperative predictors of in-hospital mortality. Results: Seventy-three of 5718 cases (1.3%) of C difficile colitis required colectomy. Mean age was 68 years. Inhospital mortality was 34% (n = 25). Eighty-six percent (n = 63) of patients received a subtotal colectomy. Patients presented with diarrhea (84%; n=61), abdominal pain (75%; n = 55), and ileus (16%; n = 12). Mean duration of symptoms was 7 days followed by 4 days of medical treatment prior to colectomy. On univariate analysis, an admitting diagnosis other than C difficile (P=.049), vasopressor requirement (P=.001), intubation (P=.001), and mental status changes (P <.001) were significant predictors of mortality. Arterial lactate level (4.9 vs 2.4 mmol/L; P=.007) was significantly higher and length of medical management (6.4 vs 3.0 days; P=.006) was significantly longer in the mortality group. Platelet counts (169 X 10(3)/mu L vs 261 X 10(3)/mu L [to convert to X 10(9)/L, multiply by 1]; P=.04) were significantly lower in the mortality group. On multivariate analysis, vasopressor requirement (P=.04; odds ratio, 5.0), mental status changes (P =.002; odds ratio, 12.6), and treatment length (P=.002; odds ratio, 1.4) remained significant predictors of mortality. Conclusions: Colectomy for C difficile colitis carries a substantial mortality regardless of patient age and white blood cell count. Preoperative vasopressor requirement, mental status changes, and length of medical treatment significantly predict mortality.