Background Necrotizing soft tissue infections (NSTIs) are rare and highly lethal. Methods Retrospective chart review of patients with NSTIs treated at 6 academic hospitals in Texas between January 1, 2004 and December 31, 2007. Patient demographics, presentation, microbiology, treatment, and outcome were recorded. Analysis of variance, chi-square, and logistic regression analysis were performed. Results Mortality rates varied between hospitals from 9 to 25% (n=296). There was significant inter-hospital variation in patient characteristics, microbiology, and etiology of NSTIs. Despite hospital differences in treatment, primarily in critical care interventions, patient age and severity of disease (reflected by shock requiring vasopressors and renal failure post-operatively) we the re main predictors of mortality. Conclusions Significant center differences occur in patient populations, etiology, and microbiology of NSTIs, even within a concentrated region. Management should be based on these characteristics given that adjunctive treatments are unproven and variations in outcome are likely due to patient disease at presentation. Summary Significant regional inter-hospital variations occurs in patient characteristics, microbiology, etiology, and management of necrotizing soft tissue infections (NSTIs) which impact outcome.