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Objective: To estimate the incidence and related risk factors of sepsis between road traffic injuries (RTIs) and non-RTIs. Methods: Clinical data of 339 patients with severe trauma who were admitted into ICU in both Third Affiliated Hospital of Army Military Medical University and ChongGang General Hospital from January 2012 to December 2015 were retrospectively analyzed. Twenty items of potential risk factors affecting sepsis were evaluated by univariate and multivariate Logistic Analysis with the purpose of drawing a comparison between RTI patients and non-RTI patients. Results: There were 154 cases of RTI and 185 cases of non-RTI entering the study period. The significant independent risk factor of sepsis in RTIs was SOFA 11 (OR=4.821; 95% CI=1.901-12.226; P=0.001). The significant independent risk factors of sepsis in non-RTIs were SOFA 11 (OR=12.410; 95% CI=2.559-60.185; P=0.002), tracheal intubation (OR=8.913; 95% CI=2.322-34.206; P=0.001), APACHE II 15 (OR=3.684; 95% CI=1.750-7.753; P=0.001). Conclusions: The clinical medical personnel should not give equal treatment to RTI patients and non-RTI patients admitted in ICU in that factors predicting sepsis within above two groups are different. The sample volume should be increased and validated in further prospective research. [ABSTRACT FROM AUTHOR]