Abstract Background: Traumatic brain injury is responsible for greater than 4.7 million deaths globally and 21.2 % of deaths in Ethiopia. Despite it remains a public health problem mainly affecting young adults and males in Ethiopia, studies about Predictors of in hospital mortality among traumatic brain injury are scarce. Objective: To determine predictors of in hospital mortality among adult traumatic brain injury patients in Felegehiwot comprehensive specialized hospital, Amhara region, Northwest Ethiopia, 2020. Methods: retrospective cohort study was conducted in Felegehiwot Comprehensive Specialize hospital. All cases of traumatic brain injury registered from January 1st 2015-December 30th, 2019 were included and followed retrospectively. Descriptive statistics were used to describe patient characteristics. Kaplan-Meier survival curve together with log rank test were used to test for the presence of difference in survival among groups. Cox proportional hazards regression model was used at 5% level of significance to determine the net effect of each explanatory variable on time to death. Result: A total of 338 patients aged  15 years and diagnosed as traumatic brain injury were included in the analysis. Of these, 103 patients (30.45%) were died giving a crude death rate of 22 per 1000 (95%CI: 18.02-26.51) person-days. The overall median survival time was 133 days. The overall estimated survival rate after diagnosis of traumatic brain injury was 42.76% (95%: CI: 25.77-58.73). Independent predictors of mortality after diagnosis of traumatic brain injury were; admission GCS< 8(AHR: 4.85(95% CI: 1.73-13.62), Bilateral non-reactive pupils at admission (AHR; 2.00 (95% CI: 1.10-3.71), elevated systolic blood pressure at admission AHR:0.31(95% CI:0.11-0.86),elevated diastolic blood pressure at admission (AHR: 3.54(95%CI: 1.33-9.43) and hematoma evacuation AHR: 0.42(95 % CI: 0.16- 0.90). Conclusion and recommendation; mortality rate in this study was relatively higher. Glasgow Coma Scale, bilateral non-reactive pupils, elevated blood pressure and hematoma evacuation were significant predictors of mortality. Felegehiwot Comprehensive Specialized Hospital shall give special attention to patients with the identified predictors. Further prospective follow up studies that will include residence and occupation as predictors of mortality are recommended. Key terms- Glasgow coma scale, survival status, Bair-Dar. Acronyms/Abbreviations