Road traffic collisions are a major cause of traumatic brain injury. However, the relationship between road traffic collision dynamics and traumatic brain injury risk for different road users is unknown. We investigated 2,065 collisions from Great Britain’s Road Accident In-depth Studies collision database involving 5,374 subjects (2013-20). 595 subjects sustained a traumatic brain injury (20.2% of 2,940 casualties), including 315 moderate-severe and 133 mild-probable. Key pathologies included skull fracture (179, 31.9%), subarachnoid haemorrhage (171, 30.5%), focal brain injury (168, 29.9%) and subdural haematoma (96, 17.1%). These results were extended nationally using >1,000,000 police-reported collision casualties. Extrapolating from the in-depth data we estimate that there are ~20,000 traumatic brain injury casualties (~5,000 moderate-severe) annually on Great Britain’s roads, accounting for severity differences. Detailed collision investigation allows vehicle collision dynamics to be understood and the change-in-velocity (known as delta-V) to be estimated for a subset of in-depth collision data. Higher delta-V increased the risk of moderate-severe brain injury for all road users. The four key pathologies were not observed below 8km/h delta-V for pedestrians/cyclists and 19km/h delta-V for car occupants (higher delta-V threshold for focal injury in both groups). Traumatic brain injury risk depended on road user type, delta-V and impact direction. Accounting for delta-V, pedestrians/cyclists had a 6-times higher likelihood of moderate-severe brain injury than car occupants. Wearing a cycle helmet was protective against overall and mild-to-moderate-severe brain injury, particularly skull fracture and subdural haematoma. Cycle helmet protection was not due to travel or impact speed differences between helmeted and non-helmeted cyclist groups. We additionally examined the influence of delta-V direction. Car occupants exposed to a higher lateral delta-V component had a greater prevalence of moderate-severe brain injury, particularly subarachnoid haemorrhage. Multivariate logistic regression models created using total delta-V value and whether lateral delta-V was dominant had the best prediction capabilities (area under the receiver operator curve as high as 0.95). Collision notification systems are routinely fitted in new cars. These record delta-V and automatically alert emergency services to a collision in real-time. These risk relationships could therefore inform how routinely fitted automatic collision notification systems alert the emergency services to collisions with a high brain injury risk. Early notification of high-risk scenarios would enable quicker activation of the highest level of emergency service response. Identifying those that require neurosurgical care and ensuring they are transported directly to a centre with neuro-specialist provisions could improve patient outcomes.