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Background: The effectiveness of ketamine as adjunctive or monotherapy for post-intubation sedation in adults with trauma on mechanical ventilation is unclear., Methods: A rapid review of systematic reviews of randomized controlled trials, then randomized controlled trials or observational studies was conducted searching three electronic databases (PubMed, Embase, Cochrane Library) and one clinical trial registry on June 1, 2022. We used a prespecified protocol following Cochrane rapid review methods., Results: We identified eight systematic reviews of randomized controlled trials and observational studies. Among the included reviews, only the most relevant, up to date, highest quality-assessed reviews and reviews that reported on critical outcomes were considered. Adjunctive ketamine showed a morphine sparing effect (MD -13.19 µmg kg -1 h -1 , 95 % CI -22.10 to -4.28, moderate certainty of evidence, 6 RCTs), but no to little effect on midazolam sparing effect (MD 0.75 µmg kg -1  h -1 , 95 % CI -1.11 to 2.61, low certainty of evidence, 6 RCTs) or duration of mechanical ventilation in days (MD -0.17 days, 95 % CI -3.03 to 2.69, moderate certainty of evidence, 3 RCTs).Adjunctive ketamine therapy may reduce mortality (OR 0.88, 95 % CI 0.54 to 1.43, P  = 0.60, very low certainty of evidence, 5 RCTs, n  = 3076 patients) resulting in 30 fewer deaths per 1000, ranging from 132 fewer to 87 more, but the evidence is very uncertain. Ketamine results in little to no difference in length of ICU stay (MD 0.04 days, 95 % CI -0.12 to 0.20, high certainty of evidence, 5 RCTs n  = 390 patients) or length of hospital stay (MD -0.53 days, 95 % CI -1.36 to 0.30, high certainty of evidence, 5 RCTs, n  = 277 patients).Monotherapy may have a positive effect on respiratory and haemodynamic outcomes, however the evidence is very uncertain., Conclusion: Adjunctive ketamine for post-intubation analgosedation results in a moderate meaningful net benefit but there is uncertainty for benefit and harms as monotherapy., Competing Interests: MM, CH and IK are partly supported by the Research, Evidence and Development Initiative (READ-It). READ-It (project number 300342-104) is funded by UK aid from the UK government; however, the views expressed do not necessarily reflect the UK government's official policies. Research reported in this publication is the sole responsibility of the researchers and do not reflect the official views or position of the South African Medical Research Council or the University of Stellenbosch. Authors report no conflicts of interest. MM and CH are editors of the African Journal of Emergency Medicine. Neither MM, nor CH were involved in the editorial workflow for this manuscript. The African Journal of Emergency Medicine applies a double blinded process for all manuscript peer reviews. MM is a member of the South African GRADE Network and International GRADE Working Group. MM and CH are members of the PHC/Adult Hospital Level Committee, TDL acted as the National Department of Health secreteriat during the PHC/Adult Hospital Level Committee and subsequent NEMLC review process. The authors declared no further conflict of interest., (© 2023 The Authors. Published by Elsevier B.V. on behalf of African Federation for Emergency Medicine.)