Antibiotic-associated colitis is a significant clinical problem, especially in patients hospitalized for longer than three days. Clostridium difficile is now established as the most common nosocomial enteric pathogen causing antibiotic-associated colitis. The condition rarely occurs beyond the boundaries of the large bowel, but can represent significant diagnostic and therapeutic problems if it involves bowel that is used in the creation of a diversionary reservoir such as an ileo-cecal neobladder. We present what we believe to be the first reported case of fatal pseudomembranous colitis occurring in an ileo-cecal neobladder.