Background.Infections involving skin, soft tissue, bone, or joint (SSTBJ) are common and often require hospitalization. There are currently few published studies on the epidemiology and clinical and economic outcomes of these infections, whether acquired in the community or healthcare setting, in a large population.

Objective.To characterize outcomes of culture‐proven SSTBJ infection in hospitalized patients, using information from a large database.

Design.We identified patients hospitalized in 134 institutions during 2002‐2003 for whom specific International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes and a culture‐positive SSTBJ specimen were recorded. Patients were classified into 4 clinical groups based on the type and clinical severity of infection. Patients in each group were further classified on the basis of whether their infection was community acquired or healthcare associated and whether it was complicated or uncomplicated.

Results.We identified 12,506 patients with culture‐positive infections and categorized them as having cellulitis (37.3%), osteomyelitis or septic arthritis (22.4%), surgical wound infection (26.1%), device‐associated or prosthesis infection (7.2%), or other SSTBJ infection (6.9%). Monomicrobial infection was reported for 59% of patients, 54.6% of whom had Staphylococcus aureus as the etiologic agent. Of all S. aureus isolates recovered, 1,121 (28.0%) of 4,007 were resistant to methicillin. Healthcare‐associated infections accounted for 27.2% of cases and were associated with a significantly greater mortality rate, a longer length of stay, and greater hospital charges, compared with community‐acquired infections. Patients with a complicated infection (78.4%) had a significantly greater mortality rate, a longer length of stay, and greater hospital charges, compared with patients with an uncomplicated infection.

Conclusions.SSTBJ infections are frequent among hospitalized patients. S. aureus caused infection in more than 50% of the patients studied, and 28.0% of the S. aureus isolates recovered were resistant to methicillin. Healthcare‐associated and complicated infections are associated with a significantly higher mortality rate and more prolonged and expensive hospitalizations. These findings could assist in projects to revise current management strategies in order to optimize outcomes while restraining costs.