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To determine whether a minimally invasive, colon-preserving approach could serve as an alternative to total colectomy in the treatment of severe, complicated Clostridium difficile–associated disease (CDAD).C. difficile is a significant cause of morbidity and mortality worldwide. Most cases will respond to antibiotic therapy, but 3% to 10% of patients progress to a severe, complicated, or “fulminant” state of life-threatening systemic toxicity. Although the advocated surgical treatment of total abdominal colectomy with end ileostomy improves survival in severe, complicated CDAD, outcomes remain poor with associated mortality rates ranging from 35% to 80%.All patients who were diagnosed with severe, complicated (“fulminant”) CDAD and were treated at the University of Pittsburgh Medical Center or VA Pittsburgh Healthcare System between June 2009 and January 2011 were treated with this novel approach. The surgical approach involved creation of a loop ileostomy, intraoperative colonic lavage with warmed polyethylene glycol 3350/electrolyte solution via the ileostomy and postoperative antegrade instillation of vancomycin flushes via the ileostomy. The primary end point for the study was resolution of CDAD. The matching number of patients treated with colectomy for CDAD preceding the initiation of this current treatment strategy was analyzed for historical comparison.Forty-two patients were treated during this time period. There was no significant difference in age, sex, pharmacologic immunosuppression, and Acute Physiology and Chronic Health Evaluation-II scores between our current cohort and historical controls. The operation was accomplished laparoscopically in 35 patients (83%). This treatment strategy resulted in reduced mortality compared to our historical population (19% vs 50%; odds ratio, 0.24; P = 0.006). Preservation of the colon was achieved in 39 of 42 patients (93%).Loop ileostomy and colonic lavage are an alternative to colectomy in the treatment of severe, complicated CDAD resulting in reduced morbidity and preservation of the colon.