Background: Traumatic brain injury (TBI) is a common cause of death in the Intensive care units and emergency departments with an estimated annual global mortality of 1.5 million people as a result of severe TBI. The prevalence of TBI varies according to regions. Despite this, there is limited data on the outcomes of patients following severe traumatic brain injury in southwestern Uganda. Herein, we studied the prevalence and outcome of severe traumatic brain injury at Mbarara Regional Referral Hospital (MRRH) at discharge.Methods: A retrospective chart review of all TBI over six months (August 2016 - February 2017). The primary outcome was the Glasgow Outcome Scale (GOS) score at discharge. A favorable outcome was either good recovery or moderate disability while unfavorable outcome was severe disability, persistent vegetative state or death. Bivariate and multivariate logistic regression analyses were used to determine the factors associated with GOS score at discharge. Data were analyzed using STATA v13.0.Results: A total of 196 hospital records of TBI patients were reviewed, 80 (40.8%) patients had severe TBI, with the average length of hospital stay at 4.3 ± 2.9 days. The mean patients' age was 35 ± 14 years with the most affected age group being 18 - 34 years (58.8%). The GOS score at discharge were; death (42.5%), persistent vegetative state (0%), severe disability (1.3%), moderate disability (3.8%) and good recovery (52.5%). Pupil size and response had a dose-response relationship with unfavorable outcome when both pupils were dilated and non-reactive to light and had a higher odd ratio (OR=6.05) and strongly associated with unfavorable outcome (p=0.011). However, surgery and seizure prophylaxis were significantly associated with favorable outcome (p=0.033), (p=0.016) and a lesser odd ratio (OR=0.29),(OR=0.31) of having unfavorable outcome respectively. Conclusion: Mbarara regional referral hospital, the prevalence of STBI is still high. Both surgery and seizure prophylaxis were associated with favorable outcome at discharge. However, unfavorable outcome was mainly seen amongst patients who develop a complication.