BACKGROUND AND OBJECTIVES:Attention deficits are often among the most persistent and debilitating impairments resulting from traumatic brain injury (TBI). This study examined the effects of lisdexamfetamine dimesylate (Vyvanse) in treating attention deficits due to moderate-to-severe TBI. It was the first study of lisdexamfetamine dimesylate with this population and, in fact, was the first controlled trial in this area examining a stimulant medication option other than methylphenidate. METHODS:This was a 12-week, randomized, double-blind, placebo-controlled, cross-over trial. A total of 22 rigorously selected cases were enrolled, 13 of whom completed the trial. They were 16-42 years of age and had newly acquired attention deficits persisting for 6-34 months post-injury. They were assessed on a broad range of neuropsychological and behavioural measures at baseline, 6-weeks and at 12-weeks. RESULTS AND CONCLUSIONS:Positive treatment effects were found involving selective measures of sustained attention, working memory, response speed stability and endurance and in aspects of executive functioning. No major problems with safety or tolerability were observed. Some moderating treatment effects were found from a broad range of pre-treatment subject characteristics and injury variables examined. Avenues for further research and treatment applications in this area are discussed.