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Common causes of hospitalizations in the United States are acute bacterial skin and skin-structure infections (ABSSSIs). The objectives of this retrospective study were to characterize hospitalized ABSSSI patients including comorbidities and identify the microorganisms associated with the infection.Adults (>18 years) hospitalized with 1 or more primary ABSSSI diagnosis were selected from the Cerner Health Facts electronic medical records database between 2009 and 2013. Causative microorganisms for ABSSSI and Gram-stain type were identified from microbiology culture, including patients with methicillin-resistant Staphylococcus aureus (MRSA).Of the 11,705 patients identified, 51.8% were male, with a mean age of 55 years at admission; 49.7% were obese; and 30.9% had diabetes. More than half (56.6%) of patients had no microbiology culture results. Of the patients with an identified ABSSSI-causing pathogen, 63.9% were gram-positive, including 18.4% infected with MRSA; 11.9% were gram-negative; and 24.2% had mixed infections (gram-positive and gram-negative), including 3.6% with MRSA. After adjusting for confounding variables, a significant association was noted between obesity and 30-day ABSSSI-related readmission among males, patients younger than 65 years, and patients without MRSA.Hospitalized ABSSI patients had comorbidities, including obesity, diabetes, hypertension, and depression, which can complicate antibiotic selection. Patient characteristics and pathogen coverage must be considered in antibiotic selection in ABSSSI.