Background: Soft-tissue infections traditionally have been viewed as carrying a lower risk of death than other types of infection such as pneumonia, blood stream, and intra-abdominal. The influence of secondary bacteremia on the outcomes of patients with soft-tissue infections is not well described. Objectives: To describe the risk factors for bacteremia among patients admitted to an urban medical center with soft-tissue infections and the influence of bacteremia on outcomes. Methods: A retrospective cohort study of 717 patients with culture-positive non-necrotizing soft-tissue infections admitted between April 1, 2005, and December 31, 2007. Results: Bacteremia was present in 52% of the patients. Increasing age, previous hospitalization, decubitus or lower-extremity ulcers, device-related soft-tissue infection, and polymicrobial infection were independent predictors of bacteremia. Intensive care unit admission (adjusted odds ratio [AOR] 3.57; 95% confidence interval [CI] 2.17, 5.86), lower-extremity ulcer (AOR 3.43; 95% CI 2.07, 5.70), and bacteremia (AOR 6.37; 95% CI 3.34, 12.12) were independent predictors of in-hospital death. When patients with device-related soft-tissue infections were excluded, the rate of secondary bacteremia was 37.6% (201/535), and it remained an independent predictor of in-hospital death. Conclusions: The occurrence of bacteremia in soft-tissue infections is associated with a greater risk of death. Health care providers should be aware of the risk factors for bacteremia in patients with soft-tissue infections in order to provide more appropriate initial antimicrobial therapy and to ascertain its presence as a prognostic indicator.