Our goal was to perform a systematic review of the literature on the use of ketamine in traumatic brain injury (TBI) and its effects on intracranial pressure (ICP). All articles from MEDLINE, BIOSIS, EMBASE, Global Health, HealthStar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform (inception to November 2013), reference lists of relevant articles, and gray literature were searched. Two reviewers independently identified all manuscripts pertaining to the administration of ketamine in human TBI patients that recorded effects on ICP. Secondary outcomes of effect on cerebral perfusion pressure, mean arterial pressure, patient outcome, and adverse effects were recorded. Two reviewers independently extracted data including population characteristics and treatment characteristics. The strength of evidence was adjudicated using both the Oxford and GRADE methodology. Our search strategy produced a total 371 citations. Seven articles, six manuscripts and one meeting proceeding, were considered for the review with all utilizing ketamine, while documenting ICP in severe TBI patients. All studies were prospective studies. Five and two studies pertained to adults and pediatrics, respectively. Across all studies, of the 101 adult and 55 pediatric patients described, ICP did not increase in any of the studies during ketamine administration. Three studies reported a significant decrease in ICP with ketamine bolus. Cerebral perfusion pressure and mean blood pressure increased in two studies, leading to a decrease in vasopressors in one. No significant adverse events related to ketamine were recorded in any of the studies. Outcome data were poorly documented. There currently exists Oxford level 2b, GRADE C evidence to support that ketamine does not increase ICP in severe TBI patients that are sedated and ventilated, and in fact may lower it in selected cases.