Morbidity secondary to Clostridium difficile infection (CDI) places a burden on the health care system. Updated practice guidelines for CDI have been published by the Infectious Diseases Society of America in 2010, with a supplement published in 2013 by the American College of Gastroenterology on recommendations for diagnosis, management, and prevention of CDI. Both guidelines identify a scoring system to calculate the severity of CDI, with recommended antibiotic choices based on CDI severity. The aim of this study was to evaluate the adherence to guidelines for the management of severe CDI in hospitalized patients at an academic medical center.