Objective: Etomidate and ketamine are hemodynamically stable induction agents for rapid sequence intubation (RSI) of critically ill patients. Despite their relative stability in terms of hemodynamics, how the choice of agent affects mortality and the success of the procedure is debatable and has not yet been explored via systematic review and meta-analysis. The objective of this systematic review is to compare the efficacy of ketamine and etomidate for RSI in terms of mortality, hemodynamic parameters, and success rate. Methods: A comprehensive search of PubMed, Embase, and the Web of Science was conducted from the starting date of each database until April 2024. Randomized controlled trials comparing the safety and efficacy of ketamine and etomidate as induction drugs for critically ill patients undergoing RSI were included. The primary outcome was the risk of 28-day mortality, and the secondary outcomes included the success rate and postinduction hypotension. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects meta-analysis. Results: Four studies with 1,663 patients were meta-analyzed, and no statistically significant difference between the two drugs was found for 28-day mortality (RR, 0.95; 95% CI, 0.72–1.25; heterogeneity I2=39%; level of certainty of evidence per GRADE, moderate), first-pass success rate (RR, 1.00; 95% CI, 0.97–1.03), or postinduction cardiac arrest (RR, 1.10; 95% CI, 0.62–1.96). Postinduction hypotension was higher in the ketamine group (RR, 1.30; 95% CI, 1.03–1.64), but the result was not statistically significant. Conclusion Mortality outcomes did not differ when ketamine or etomidate was used for RSI in critically ill patients. Ketamine, however, was associated with a non-significantly higher risk of postinduction hypotension.