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Current guidelines recommend blood cultures in skin and soft-tissue infection (SSTI) patients only with signs of systemic toxicity and wound cultures for severe purulent infections. Our objectives were to determine: 1) blood and wound culture yields in patients admitted with SSTIs; 2) whether injection drug users (IDUs) and febrile patients had higher blood culture yields; and 3) whether blood and wound cultures grew organisms sensitive to typical SSTI empiric antibiotics.We prospectively enrolled adult patients admitted from the ED with SSTIs at an urban hospital. We recorded patient characteristics, including IDU, comorbidities and temperatures, and followed admitted patients throughout their hospital course.Of 734 SSTI patients enrolled, 246 (33.5%) were admitted. Of 86 (35.0%) patients who had blood cultures, six had positive cultures (yield = 7.0%; 95% confidence intervals [CIs] 3.2–14.4); 4 were methicillin sensitive Staphylococcus aureus (MSSA) and 2 were methicillin resistant (MRSA). Of 29 febrile patients, 1 had a positive culture (yield = 3.5%; 95% CI 0.6–17.2). Of 101 admitted IDU patients, 46 (46%) received blood cultures, and 4 had positive cultures (yield = 8.7%; 95% CI 3.4–20.3).Of 89 patients with purulent wounds, 44 (49.4%) patients had ED wound cultures. Thirteen had positive cultures (yield = 29.6%; 95% CI 18.2–44.2%). Most were MRSA, MSSA, and group A Streptococcus species — all sensitive to Vancomycin.Febrile and IDU patients had low yields of blood cultures similar to yields in non-IDU and afebrile patients. All blood and wound culture species were adequately covered by currently recommended empiric antibiotic regimens.