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This review investigates the potential of the renin-angiotensin system (RAS) as a treatment pathway for TBI in adults. Relevant electronic databases were searched on December 18, 2019, and updated May 16, 2021. All English language articles with adult human or animal populations investigating RAS drugs as an intervention for TBI or reporting genetic evidence relevant to the RAS and TBI were screened. Eighteen pre-clinical randomized controlled trials (RCTs) (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u20092269) and two clinical cohort studies (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u2009771) were included. Meta-analyses of six pre-clinical RCTs (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u200999) indicated that candesartan improved neurological function over the short term (&lt; 7 days: standardized mean difference [SMD] 0.61, 95% confidence interval [CI] 0.19\u20131.03, I2\u2009=\u20090%) and over the long term (\u2265 7 days: SMD 1.06, 95% CI 0.38; 1.73, I2\u2009=\u20090%) post-TBI. Findings were similar for most secondary outcomes. There was a suggestion of benefit from other RAS-targeting drugs, although evidence was limited because there were few small studies. There was insufficient evidence to enable strong assessment of these drugs on mortality post-TBI. We conclude that angiotensin-receptor blockers, especially candesartan, show positive outcomes post-TBI in pre-clinical studies with moderate quality of evidence (Grading of Recommendations Assessment, Development and Evaluation [GRADE]). More research into the effect of regulatory-RAS targeting drugs is needed. Clinical trials of candesartan following TBI are recommended, because there is strong and consistent evidence of neuroprotection shown by these pre-clinical studies.\n                  <\/jats:p>","DOI":"10.1089\/neu.2021.0401","type":"journal-article","created":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T08:21:42Z","timestamp":1642148502000},"page":"473-486","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Renin Angiotensin System as a Potential Treatment Target for Traumatic Brain Injury: A Systematic Review and Meta-Analysis"],"prefix":"10.1177","volume":"39","author":[{"given":"Daniel H.","family":"Baron","sequence":"first","affiliation":[{"name":"Translational Health Sciences and University of Bristol, Bristol, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivia A.","family":"Skrobot","sequence":"additional","affiliation":[{"name":"Translational Health Sciences and University of Bristol, Bristol, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer C.","family":"Palmer","sequence":"additional","affiliation":[{"name":"Population Health Sciences, Bristol Medical School, and University of Bristol, Bristol, United Kingdom."},{"name":"MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kanchan","family":"Sharma","sequence":"additional","affiliation":[{"name":"Translational Health Sciences and University of Bristol, Bristol, United Kingdom."},{"name":"Department of Neurology, Southmead Hospital, North Bristol NHS Trust, Bristol, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick G.","family":"Kehoe","sequence":"additional","affiliation":[{"name":"Translational Health Sciences and University of Bristol, Bristol, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2022,3,23]]},"reference":[{"key":"e_1_3_5_2_2","volume-title":"Traumatic Brain Injury and Offending: An Economic Analysis","author":"Parsonage M.","year":"2016","unstructured":"Parsonage M. 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