Background: Traditionally, skin and skin structure infections (SSSIs) have been viewed as having a lower risk of mortality, morbidity, and cost compared with other types of infection. The influence of secondary bacteremia on the medicoeconomic outcomes of patients with SSSIs has not been well described. Objective: The goal of this study was to evaluate the impact of bacteremia complicating SSSIs on length of hospital stay and costs. Methods: This was a retrospective cohort study involving 579 patients with culture-positive SSSIs who were admitted to Barnes-Jewish Hospital, a major academic medical center, between April 1, 2005, and December 31, 2007. The outcomes evaluated in this analysis included hospital mortality, length of stay, hospital costs, and hospital readmission. Results: Secondary bacteremia was present in 277 (47.8%) patients. Hospital mortality was statistically greater among patients with bacteremia (7.9% vs 1.0%; P < 0.001). The unadjusted median length of stay in bacteremic patients was 7.1 days compared with 2.8 days in those without bacteremia (P < 0.001 by log-rank test). This finding correlated with total hospital costs, which were greater in patients with bacteremia (median values: $14,623 vs $5841.50; P < 0.001). In a Cox model controlling for multiple confounders, bacteremia independently correlated with hospital duration (adjusted hazard ratio [HR], 1.820; 95% CI, 1.654-2.003; P < 0.001) and hospital costs (adjusted HR, 1.895; 95% CI, 1.723-2.083; P < 0.001). Hospital readmission within 30 days of discharge was also significantly more common among patients with SSSIs complicated by bacteremia (24.5% vs 12.9%; P < 0.001). Conclusions: Bacteremia complicating SSSIs occurred in almost 50% of patients infected with gram-positive bacteria in our institution. Beyond its impact on mortality, bacteremia is associated with increased length of stay, hospital costs, and readmission. However, these data are from a single academic medical center and may not be adjusted for all applicable confounders.