PURPOSE:Reports of fatality related toClostridium difficilecolitis and a sharp increase in prevalence of this infection prompted a study of patients who develop a more aggressive form of this disease.METHODS:Over 38 months, 710 patients at our institution developedC. difficilecolitis. Twenty‐one (3 percent) of these patients either required intensive care unit admission or died as a result of their infection. A retrospective, case‐controlled study was undertaken to compare these patients, who were considered to have severeC. difficilecolitis, with the remaining patients with milder disease.RESULTS:Factors that predisposed to the development of severeC. difficilecolitis included intercurrent malignancy, chronic obstructive pulmonary disease, immunosuppressive and antiperistaltic medications, renal failure, and administration of clindamycin(P<0.05 for all). Patients with severeC. difficilecolitis were more likely to have abdominal pain, tenderness and distention, peritonitis, hemoconcentration (>5 points), hypoalbuminemia (<3 mg/dl), and elevated or suppressed white blood cell count (>25,000; <1,500;P<0.05 for all). These factors were used to create a scoring system that could distinguish between patients with severeC. difficilecolitis and those with mild disease. Thirteen patients in the late stages of terminal illness with metastatic malignancy or age >90 were considered poor or inappropriate surgical candidates. Only the remaining eight patients could have potentially recovered from operation with hope for long‐term survival. Of these, seven were treated without colonic resection, and six of the seven survived, whereas one patient underwent colectomy and did not survive.CONCLUSIONS:Patients with severeC. difficilecolitis can be readily identified. Often they have coexisting illness that precludes operation. In this series, only 1 of 21 patients with severeC. difficilemight have benefited from an aggressive surgical approach.