BACKGROUND: Traumatic brain injury (TBI) is a leading cause of injury-related disability and death globally, which negatively affects individuals, families, and society. Predicting the risk for mortality among TBI patients is crucial in guiding further timely and effective treatment plans. Both the standard risk assessment tools and blood-based biomarkers are helpful in predicting outcomes among TBI patients. However, no studies have compared the predicting performance of the individual and combined indicators from the two major types. AIM: This study aimed to compare the Modified Early Warning Score (MEWS), Red blood cell distribution width (RDW), and creatine in predicting 7-day mortality among TBI patients. METHODS: A retrospective study was conducted in the emergency department of the First People's Hospital of Changde, China, from January 1, 2023, to June 30, 2023. Data of 1,701 patients with TBI were obtained from the hospital's electronic medical records. A logistic regression model was used to determine independent factors influencing 7-day mortality. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) was calculated to compare the individual and combined effects of MEWS, RDW, and creatine in predicting 7-day mortality based on bootstrap resampling (500 times). RESULTS: Among the 1,701 patients, 225 died, with a mortality rate of 13.23%. The multivariate analysis showed that the type of TBI lesion, MEWS, SBP, DBP, MAP, SpO CONCLUSION: MEWS performed best in predicting the 7-day mortality of TBI patients, and its predicting performance was improved when combined with blood-based biomarkers such as RDW and creatine. Our findings provide preliminary evidence supporting the combination of MEWS with blood-based biomarkers as a new method for predicting 7-day mortality in patients with TBI.