OBJECTIVES: To determine the additional costs and lengths of stay (LOS) attributable to complicated skin and soft tissue infections (cSSI) for patients admitted to Thomas Jefferson University Hospital, an urban academic tertiary care hospital. METHODS: All patients admitted between January 1, 2003 and December 31, 2003 were identified using the hospital billing system. Patients with a potential cSSI were identified using the specific ICD-9 diagnosis codes. Costs of care and lengths of stay, based on the hospital's true cost accounting system, were compared by Diagnosis Related Group (DRG) between the cSSI population and the non-cSSI population. RESULTS: Of the 33,764 patient discharges in 2003, 1,883 (5.5%) included one of the cSSI diagnosis codes; these encompassed 225 DRGs. The mean cost for cSSI cases was $20,965 higher than for non-cSSI cases, and mean LOS was ten days higher for cSSI cases. For surgical and medical DRGs, mean cost of cSSI added $42,563 onto the cost for cases in surgical DRGs compared to an average increase of $10,048 added to cost of medical DRGs. Differences in costs and LOS were observed in analyses by Major Disease Categories (MDCs) and individual DRGs as well. For MDCs, myeloproliferative disorders, multiple trauma, and diseases of the nervous system, costs were $68,027, $48,286, and $27,496, higher for the cSSI cases, respectively. This difference was also reflected in additional days of stay of 22, 11, and 14 days, respectively. For patients with cSSI, the three specific DRGs responsible for the maximum total health care dollars expended were bone marrow transplants, rehabilitation, and small and large bowel procedures. CONCLUSIONS: cSSIs significantly increase hospital resource consumption and costs. The difference in costs is especially pronounced for patients undergoing surgical procedures. Results suggest that measures taken to avoid or more effectively treat cSSIs could yield significant savings to hospitals.