Amnesia is a common sequela following traumatic brain injury (TBI), for which there is no current treatment. Pleiotropic effects of statins have demonstrated faster recovery of spatial memory after TBI in animals. We conducted a double-blind randomized clinical trial add-on of patients with TBI (16-50 years of age), with Glasgow Coma Scale (GCS) scores of 9-13, and intracranial lesions as demonstrated by computed tomography (CT) scan. We excluded those patients with recent head injury or severe disability; administration of known drugs as modifiers of statin metabolism; multisystemic trauma; prior use of mannitol, barbiturate, corticosteroids, indomethacin or calcium antagonists; surgical or isolated lesion in brainstem; allergy to statins; previous hepatopathy or myopathy; previous management in another clinic; or pregnancy. Each patient received the same treatment and was randomly allocated to receive either rosuvastatin (RVS) or placebo over a period of 10 days. The primary outcome measures assessed were amnesia and disorientation times using Galveston Orientation Amnesia Test. Additionally, we evaluated plasma levels of interleukin (IL) 1beta, tumor necrosis factor (TNF) alpha, and IL-6, as well as disability at 3 months. We analyzed eight patients with RVS and 13 controls with similar basal characteristics. Using Cox regression analysis, administration of RVS showed a reduction of amnesia time with a hazard ratio of 53.76 (95% confidence interval [CI], 1.58-1824.64). This was adjusted for early intubation, basal leukocytes, basal Marshall and Fisher score, change of IL-1beta levels, and lesion side. IL-6 values at day 3 were increased in the RVS group (p = 0.04). No difference was detected in disability at 3 months. While statins may reduce amnesia time after TBI, possibly by immunomodulation, further trials are needed in order to confirm this positive association.