Necrotizing soft tissue infections (NSTIs) are a major source of morbidity and mortality, yet predictors of mortality for these critically ill patients remain poorly characterized. The aim of this study was to identify risk factors for mortality in patients with NSTI. We performed a retrospective review of all patients presenting with an NSTI to our county-funded, academic medical center between 2008 and 2013. Admission characteristics, comorbidities, laboratory values, time to operation, and perioperative cultures were assessed to identify predictors of mortality. During the 5-year study period, 138 patients were admitted with a NSTI; 20 (14.5%) of the patients died. Univariate predictors of mortality included bandemia, elevated creatinine, low bicarbonate, elevated lactate, a lower admission temperature, and shorter duration of presenting symptoms. Using Classification And Regression Tree analysis and subsequent logistic regression, bands greater than 25 per cent (odds ratio [OR], 8.0; 95% confidence interval [CI], 2.7 to 24.1; P = 0.0002), duration of symptoms less than 3.5 days (OR, 4.0; 95% CI, 1.2 to 13.9; P = 0.03), and temperature 37 degrees C or less (OR, 3.6; 95% CI, 1.1 to 11.8; P = 0.03) were found to be independent predictors of mortality. Awareness of these predictors should prompt aggressive management of this at-risk population.