Neuroprotective treatments that have shown promise in reducing secondary injury and improving recovery in animal models of traumatic brain injury (TBI) have not been found effective to date in humans. One reason may be the delay after injury in initiating treatment. Statin medications are among the promising neuroprotective agents in animal models, and their presence in the bloodstream of many individuals at the time of injury might optimize their clinical impact. This observational study conducted by a subset of centers participating in the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR)-funded TBI Model System program sought to examine the effects of taking statin medication at the time injury on functional outcomes. Participants >50 years of age were prospectively enrolled during patient rehabilitation. Demographic data, cardiovascular history, and brain injury history were obtained through chart abstraction and interview. Prescription medication use in the year prior to enrollment was determined from a national pharmacy search service. Propensity scoring was used to create 49 pairs of participants who were well matched on demographic and clinical attributes but discordant for statin use. The treated and untreated participants did not differ on initial Glasgow Coma Score, time until commands were followed, duration of post-traumatic amnesia, or Functional Independence Measure (FIM) scores at rehabilitation admission, discharge, or 1 year post-injury, or on acute or rehabilitation hospital lengths of stay. Evidence of greater and lesser statin compliance was not associated with outcome. This study did not provide support for a clinically important benefit of statin use at the time of moderate to severe TBI.