Background: Clostridium difficile is the principal cause of infectious diarrhea in hospitalized patients. The aim of this study was to describe and compare length of stay (LOS), costs, and in-hospital deaths for C difficile infection (CDI) and non-CDI hospitalizations, in a cohort of middle-aged and older Australians. Methods: We used survey data from the 45 and Up Study, linked to hospitalization and death data. We calculated the average LOS and costs per hospitalization, and the proportion of in-hospital deaths for CDI and non-CDI hospitalizations. We then compared hospitalizations with CDI as a secondary diagnosis to non-CDI hospitalizations by stratifying hospitalizations based on principal diagnosis and then using generalized linear models to compare LOS and in-hospital costs, and logistic regression for in-hospital deaths, adjusting for age and sex. Results: There were 641 CDI hospitalizations during 2006-2012. The average LOS was 17 days; the average cost per hospitalization was AUD 12,704; and in 7.3% of admissions (47 out of 641) the patient died. After adjusting for age and sex, hospitalizations with CDI were associated with longer LOS, higher costs, and a greater proportion of in-hospital deaths compared with hospitalizations with similar principal diagnosis but without CDI. Conclusions: CDI places additional burden on the Australian hospital system, with CDI patients having relatively lengthy hospital stays and high costs.