OBJECTIVE: This study aimed to determine the factors associated with mortality among patients with necrotizing soft tissue infection (NSTI) in Japan using inpatient data from the Diagnosis Procedure Combination (DPC) Database. METHODS: We conducted a cross-sectional study using a population retrieved from the Japanese DPC inpatient database of patients who underwent surgical operations from 2014 through 2017. The associations between the covariates and mortality were estimated using multivariate logistic regression models. RESULTS: In total, 4597 patients were registered in this study, with an overall mortality rate of 6.9%. Multilevel logistic regression analysis revealed that higher age, lower body mass index (BMI < 18.5 kg/m2), pre-existing cancer diagnosis, sepsis at admission, maintenance dialysis, antithrombin III use, and anti-methicillin-resistant Staphylococcus aureus (MRSA) antibiotic use were associated with a high mortality rate among NSTI patients. However, sex, underlying diabetes mellitus, ambulance use at admission, intravenous immunoglobulin use, higher hospital case volume, and frequency of operations were not associated with mortality. CONCLUSION: This study is the first to report the association of lower BMI, antithrombin III use, and anti-MRSA antibiotic use with a higher mortality rate among NSTI patients.