Background: Headache (HA) following traumatic brain injury (TBI) is common, but predictors and time course are not well established, particularly after moderate to severe TBI. Methods: A prospective, longitudinal cohort study of HA severity post-TBI was conducted on 450 participants at seven participating rehabilitation centers. Generalized linear mixed-effects models (GLMMs) were used to model repeated measures (months 3, 6, and 12 post-TBI) of two outcomes: HA density (a composite of frequency, duration, and intensity) and HA disruptions to activities of daily living (ADL). Results: Although HA density and ADL disruptions were nominally highest during the first three months post-TBI, neither showed significant changes over time. At all time points, history of pre-injury migraine was by far the strongest predictor of both HA density and ADL disruptions (odds ratio (OR)=8.0 and OR=7.2, averaged across time points, respectively). Furthermore, pre-injury non-migraine HA (at three and six months post-TBI), penetrating-type TBI (at six months post- TBI), and female sex (at six and 12 months post-TBI) were each associated with an increase in the odds of a more severe HA density. Severity of TBI (post-traumatic amnesia (PTA) duration) was not associated with either outcome. Conclusion: Individuals with HA at three months after moderate-severe TBI do not improve over the ensuing nine months with respect to HA density or ADL disruptions. Those with pre-injury HA, particularly of migraine type, are at greatest risk for HA post-TBI. Other independent risk factors are penetrating-type TBI and, to a lesser degree and postacutely only, female sex. Individuals with these risk factors should be monitored and considered for aggressive early intervention. © 2013 International Headache Society.