Traumatic brain injury (TBI) is an important cause of morbidity and mortality especially in low-and-middle income countries. The objective was to assess causes and outcomes in TBI patients presenting to a tertiary-care hospital in Uganda. This prospective observational study was conducted at Mulago National Referral Hospital, Kampala, Uganda for 15 months during 2016–17. Patients of all age groups presenting to the emergency department of the hospital with suspected or documented TBI were enrolled into the study. Patient demographics, TBI causes and outcomes were recorded. TBI was grouped into mild, moderate and severe categories based on Glasgow Coma Scale (GCS). Ethical approval was taken from Johns Hopkins School of Public Health and Makerere University. Intent was known for 3749 TBI patients, of these 69.7% (n=2614) presented with unintentional TBI. About 84.8% were males; mean age was 28.6±14.1 years with 71.9% between the ages of 19–45 years. The main causes of unintentional TBI were road traffic injuries (RTIs) (87.9%) and falls (11%). Pedestrians (42.3%) and motorcycle drivers (28.1%) were common road users. Only 16.5% of RTI patients were wearing helmet at the time of the crash. About 47.2% of the RTIs involved a car and 34.3% involved boda-boda (motorcycle-taxi). Around 16.5% of RTI patients and 23.3% of fall patients had GCS below 8. About 43.6% of the patients were admitted to ward, 34.0% were sent home. There were 73 deaths; 63 were RTI patients and 10 had a fall. Unintentional TBI is common among young males in Kampala with RTI being the main cause of TBI. RTI is an important cause of unintentional TBI among young males in Kampala. This has implications for vulnerable road users including pedestrians and motorcycle riders. Having designated pedestrian crossing for pedestrians and mandatory helmet use can reduce cases of TBI caused by RTIs.