We aimed to describe and quantify the relationship between cause of injury and final outcome following traumatic brain injury (TBI). Individual patient data (N = 8708) from eight therapeutic Phase III randomized clinical trials in moderate or severe TBI, and three TBI surveys were used to investigate the relationship between cause of injury and outcome, as assessed by the Glasgow Outcome Scale (GOS) at 6 months. Proportional odds methodology was applied to quantify the strength of the association and expressed as an odds ratio in a meta-analysis. Heterogeneity across studies was assessed and associations with other predictive factors explored. In a univariate analysis, a strong association between the cause of injury and long-term outcome in moderate to severe TBI patients was observed, with consistent results across the studies. Road traffic accidents (OR 0.66, 95% CI 0.60-0.73), assaults (OR 0.66, 95% CI 0.52-0.84), and injuries sustained during sporting or recreational activities (OR 0.45, 95% CI 0.28-0.71) were all associated with better outcomes than the reference category of falls. Falls were found to be associated with an older age and with a higher incidence of mass lesions. Following adjustment for age in the analysis, the relationship between cause of injury and outcome was lost. © Mary Ann Liebert, Inc.