The choice of drug used to facilitate endotracheal intubation in trauma patients during rapid sequence induction (RSI) may have an impact on survival. Ketamine is commonly used in the hemodynamically unstable trauma patient although it has been associated with side effects. This review sought to investigate whether ketamine should be preferred over other induction agents for RSI in trauma patients. PubMed, Embase, and the Cochrane Library were systematically searched on September 19, 2016 for studies reporting RSI of adult trauma patients with ketamine compared with another induction agent (etomidate, propofol, thiopental, or midazolam). No language restrictions were applied. The primary outcome was 30-day mortality, and secondary outcomes included information on blood transfusions, length of hospital stay, and hospital mortality. Risk of bias was assessed using the Cochrane Risk of Bias assessment tool for randomized trials and the Risk of Bias in Non-Randomized Studies of Interventions for nonrandomized studies of intervention. A total of 4 studies were included. A cohort study from 1976 compared thiopental (n = 26) with ketamine (n = 14) for RSI in trauma patients. The primary outcome was number of blood transfusions, and no significant difference was found. Risk of bias was judged to be serious. A randomized controlled trial from 2009 compared etomidate (n = 57) with ketamine (n = 47) and found no significant difference in 28-day mortality (odds ratio [OR], 0.8 [0.4-2.0]). The trial was judged to have a low risk of bias. Two cohort studies from 2015 and 2017 also compared etomidate (n = 116 and n = 526) with ketamine (n = 145 and n = 442). No significant difference in hospital mortality between the groups was observed (OR, 1.11 [0.38-3.27] and OR, 1.41 [0.91-2.16], respectively). Both studies were judged to have a moderate risk of bias, thus excluding the possibility of a meaningful meta-analysis. The study from 2017 also reported number of units of blood transfused during the first 48 hours after trauma and length of hospital stay. No significant differences were observed (OR, 1.14 [0.87-1.49] and OR, 1.1 [0.95-1.27], respectively). Extremely few studies have compared induction agents for RSI in trauma patients. No significant differences have been found in mortality, length of hospital stay, or number of blood transfusions after induction with ketamine compared to other induction agents, but a clinically relevant benefit or harm cannot be excluded.