In an attempt to determine the association of potential risk factors and an increase in the rate of Clostridium difficile-associated diarrhea (CDAD) at a tertiary teaching institution in the Midwest United States, all CDAD cases among admissions from a period of 20 consecutive months were analyzed. A retrospective chart review was performed on 4992 admissions from this period. Logistic regression analysis suggested a correlation between CDAD and multiple factors.