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Early operative debridement is a major determinant of outcome in necrotizing fasciitis. However, early recognition is difficult clinically. We aimed to develop a novel diagnostic scoring system for distinguishing necrotizing fasciitis from other soft tissue infections based on laboratory tests routinely performed for the evaluation of severe soft tissue infections: the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score.Retrospective observational study of patients divided into a developmental cohort (n = 314) and validation cohort (n = 140)Two teaching tertiary care hospitals.One hundred forty-five patients with necrotizing fasciitis and 309 patients with severe cellulitis or abscesses admitted to the participating hospitals.None.The developmental cohort consisted of 89 consecutive patients admitted for necrotizing fasciitis. Control patients (n = 225) were randomly selected from patients admitted with severe cellulitis or abscesses during the same period. Hematologic and biochemical results done on admission were converted into categorical variables for analysis. Univariate and multivariate logistic regression was used to select significant predictors. Total white cell count, hemoglobin, sodium, glucose, serum creatinine, and C-reactive protein were selected. The LRINEC score was constructed by converting into integer the regression coefficients of independently predictive factors in the multiple logistic regression model for diagnosing necrotizing fasciitis. The cutoff value for the LRINEC score was 6 points with a positive predictive value of 92.0% and negative predictive value of 96.0%. Model performance was very good (Hosmer-Lemeshow statistic, p = .910); area under the receiver operating characteristic curve was 0.980 and 0.976 in the developmental and validation cohorts, respectively.The LRINEC score is a robust score capable of detecting even clinically early cases of necrotizing fasciitis. The variables used are routinely measured to assess severe soft tissue infections. Patients with a LRINEC score of ≥6 should be carefully evaluated for the presence of necrotizing fasciitis.