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Acute bacterial skin and skin structure infections (ABSSSI) are common infections within the local community, and they result in higher morbidity and health care costs. While risk factors for skin and soft tissue infections have been previously evaluated, risk factors associated with secondary bloodstream infections (BSI) has not been investigated, especially in an intercity patient population with limited health care resources. In this case control investigation, 392 patients consisting of 196 cases (ABSSSI + BSI) and 196 controls (ABSSSI) were investigated to determine risk for BSI. Both sociodemographic and underlying conditions were evaluated. According to bivariate analysis of cases and controls, individuals with ABSSSI + BSI were significantly older (p < 0.001), more often male (p = 0.008), and had a higher percentage of abnormal symptoms, such as elevated temperature, white blood cell count, and acute renal failure on hospital admission (p < 0.001). Individuals with ABSSSI + BSI also had a higher percentage of chronic renal failure (p = 0.002), diabetes (p = 0.005), congestive heart failure (p = 0.012), intravenous drug use (p =0.012), and a history of prior hospitalization (p < 0.001). Several of these factors remained statistically significant by logistic regression analysis, such as male gender aOR of 1.85, 95% CI 1.11-3.66; acute renal failure aOR 2.08, 95% CI 1.18-3.67; intravenous drug use aOR 4.38, 2.22-8.62; and prior hospitalization aOR 2.41, 95% CI 1.24-4.93. This study contributes to positive social change by identifying patient characteristics that are associated with ABSSSI-related BSI, thus providing health care providers the ability to improve patient outcomes in this underserved patient population.