Background. The incidence of Clostridium difficile-associated disease (CDAD) is increasing. There are few data on the short-term and long-term attributable costs of CDAD. The objective of this study was to determine the acute and 180-day attributable inpatient costs of CDAD. Methods. We performed a retrospective cohort study of all patients without operating room costs who were admitted for ≥48 h to Barnes-Jewish Hospital, a tertiary care hospital in St. Louis, Missouri, 1 January 2003-31 December 2003 (n = 24,691). Attributable costs of CDAD were determined by multivariable linear regression and propensity-score matched-pairs analyses (n = 684) for the hospitalization in which CDAD occurred and per patient over a 180-day period, including the initial hospitalization. Results. CDAD was associated with $2454 (95% confidence interval, $2380-$2950; increase in cost, 41%) attributable costs per CDAD episode by linear regression and with $3240 attributable costs (P < .001; increase in cost, 33%) by propensity-score matched-pairs analysis. CDAD was associated with $5042 (95% confidence interval, $3797-$6481; increase in cost, 53%) attributable inpatient costs over 180 days by linear regression and with $7179 attributable costs for inpatient care (P < .001; 48% increase in costs) by propensity-score matched-pairs analysis. Conclusions. CDAD was associated with a significant increase in costs for inpatient care and increased costs at 180 days after the initial hospitalization when the CDAD episode occurred.