Aims/hypothesis Skin and soft tissue infections (SSTIs) cause substantial morbidity in persons with diabetes. There are few data on pathogens or risk factors associated with important outcomes in diabetic patients hospitalised with SSTIs. Methods Using a clinical research database from CareFusion, we identified 3,030 hospitalised diabetic patients with positive culture isolates and a diagnosis of SSTI in 97 US hospitals between 2003 and 2007. We classified the culture isolates and analysed their association with the anatomic location of infection, mortality, length of stay and hospital costs. Results The only culture isolate with a significantly increased prevalence was methicillin-resistant Staphylococcus aureus (MRSA); prevalence for infection of the foot was increased from 11.6 to 21.9% (p<0.0001) and for non-foot locations from 14.0% to 24.6% (p=0.006). Patients with non-foot (vs foot) infections were more severely ill at presentation and had higher mortality rates (2.2% vs 1.0%, p<0.05). Significant independent risk factors associated with higher mortality rates included having a polymicrobial culture with Pseudomonas aeruginosa (OR 3