We analyzed the Spanish hospital discharges registered from 1997 to 2005 with patient diagnoses of "intestinal infection due to Clostridium difficile." The mean annual incidence rate was 41.2 diagnoses per 100,000 discharges. A significant increase was found from 1997 to 2005 (slope of the regression line [b], 5.12; P < .001). Overall rates were 2.5 times as high in the group of patients aged at least 65 years as in the group aged 45-64 years.