In this prospective cohort study of patients admitted to hospitals in Quebec and Ontario, 2.8% of patients had Clostridium difficile infection and 3.0% had asymptomatic C. difficile colonization during hospitalization. Most patients with C. difficile infection had the NAP1 strain. Clostridium difficile is the leading cause of health care–associated infectious diarrhea. 1 After exposure to C. difficile, some patients remain asymptomatic, whereas others have illness ranging from mild diarrhea to fulminant colitis. 2 Outbreaks of C. difficile infection in North America and Europe have been attributed to the emergence of an epidemic strain (North American pulsed-field gel electrophoresis PFGE type 1 NAP1). 3 , 4 Risk factors for C. difficile infection include antibiotic use, advanced age, increased severity of underlying illness, prior hospitalization, use of feeding tubes, gastrointestinal surgery, and use of proton-pump inhibitors. 5 , 6 Variability in host factors may explain the wide spectrum . . .