Objective. Healthcare-associated infections are likely to be caused by drug-resistant and possibly mixed organisms and to be treated with inappropriate antibiotics. Because prompt appropriate treatment is associated with better outcomes, we studied the epidemiology of healthcare-associated complicated skin and skin-structure infections (cSSSIs). patients. Persons hospitalized with cSSSI and a positive culture result. methods. We conducted a single-center retrospective cohort study from April 2006 through December 2007. We differentiated healthcareassociated from community-acquired cSSSIs by at least 1 of the following risk factors: (1) recent hospitalization, (2) recent antibiotics, (3) hemodialysis, and (4) transfer from a nursing home. Inappropriate treatment was defined as no antimicrobial therapy with activity against the offending pathogen(s) within 24 hours after collection of a culture specimen. Mixed infections were those caused by both a grampositive and a gram-negative organism. results. Among 717 hospitalized patients with cSSSI, 527 (73.5%) had healthcare-associated cSSSI. Gram-negative organisms were more common (relative risk, 1.24 [95% confidence interval, 1.14-1.35) and inappropriate treatment trended toward being more common (odds ratio, 1.29 [95% confidence interval, 0.85-1.95]) in healthcare-associated cSSSI than in community-acquired cSSSI. Mixed cSSSIs occurred in 10.6% of patients with healthcare-associated cSSSI and 6.3% of those with community-acquired cSSSI (P =.082) and were more likely to be treated inappropriately than to be nonmixed infections (odds ratio, 2.42 [95% confidence interval, 1.43-4.10]). Both median length of hospital stay (6.2 vs 2.9 days; P <.001) and mortality rate (6.6% vs 1.1%; P =.003) were significantly higher for healthcare-associated cSSSI than community-acquired cSSSI. conclusions. Healthcare-associated cSSSIs are common and are likely to be caused by gram-negative organisms. Mixed infections carry a >2-fold greater risk of inappropriate treatment. Healthcare-associated cSSSIs are associated with increased mortality and prolonged length of hospital stay, compared with community-acquired cSSSIs.