Controversy exists as to the appropriate management of fulminant C. difficile-associated pseudomembranous colitis (PMC). We reviewed our most recent 5-year experience with 191 patients with PMC. Nine patients had an initial presentation of a surgical abdomen with clinical signs of peritonitis, elevated white blood cell count, and eight had received antibiotics prior to presentation. Two patients were placed on no cardiopulmonary resuscitation status at admission to the surgical intensive care unit; both died within 24 hours. The remaining seven patients had exploratory laparotomies. The four who had total abdominal colectomies with ileostomies recovered promptly. Two of the other three had no resection because there was edema of the colon, but no other gross pathological changes. The third had only a segmental colon resection. All three deteriorated postoperatively, and two were dead within 48 hours. The remaining patient was returned to the operating room 48 hours after the first procedure, and an abdominal colectomy and ileostomy was performed. She never recovered, however, and died 12 days later. We conclude that although most patients with PMC can be treated effectively medically, total abdominal colectomy with ileostomy is indicated when signs of peritonitis occur, even if the only finding at laparotomy is edema of the colon.