OBJECTIVES: Identify new CDAD cases, readmission rate and estimate cost over one year. METHODS: All CDAD cases were identified in Massachusetts discharge data using ICD-9-CM codes and patient identifiers. Index stays occurred from October 31, 2001 - September 30, 2002. The new case cohort excluded patients with CDAD-related admissions in the previous year. For primary CDAD cases (principal diagnosis: CDAD), all stay costs (accommodations and ancillaries) were deemed related. For secondary CDAD cases, APR-DRG assignment, severity and length of stay (LOS) were used to calculate the incremental care costs due to CDAD. All charges were adjusted (cost-to-charge, inflation, geography) to reflect national costs (2005 US$). RESULTS: The 4,015 new cases of CDAD identified reflect a prevalence of 1% among hospitalized patients. Almost all (93%) hospitals treated 1 case (range: 1-312). Of 1,310 primary CDAD cases, 66% were female, with mean age of 72 years (± 17.2), mean LOS of 6.9 days (median: 5) and mean cost of $10,260 (median: $5,752) per stay. Secondary CDAD (2,705 cases) was similar demographically but led to longer stays (mean: 15.7, median: 11 days); suffered higher (p<0.001) inpatient case fatality rates (13% vs. 5%); and were more expensive than primary cases (mean: $32,352, median: $16,842). For secondary cases, CDAD-related costs comprised 40% ($12,999) of total mean cost. Over one year, 18% of index stay survivors were readmitted for CDAD, within 51 days on average (mean 1.3 readmissions per patient, range: 1-6). Total one-year inpatient cost for CDAD management was estimated at $56 million. CONCLUSIONS: CDAD has both clinical and economic consequences. It is widespread in hospitals, generates substantial care costs for those admitted for CDAD management, and increases inpatient costs dramatically when it occurs as a complication. Recurrent CDAD leads to re-hospitalization, typically within two months, further increasing the cost burden of CDAD.