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Introduction: Rapid sequence intubation remains the cornerstone of emergency airway management. The optimal choice between these agents remains uncertain in critical care literature. We aimed to evaluate mortality differences and clinical outcomes between these agents in critically ill patients requiring emergency airway management at our institution. Methods: This single-center retrospective cohort chart review examined adult patients receiving either etomidate or ketamine for RSI between Dec 2023 to Dec 2024. The primary outcome was 7-day all-cause mortality. Secondary outcomes included 28-day mortality, vasopressor requirements within 24 hours of intubation, ventilation duration, and ICU length of stay. Safety outcomes assessed incidence of newly diagnosed adrenal insufficiency. Patients were excluded if they had known adrenal insufficiency, required intubation without sedation, known allergies to either medication, or pregnant. Chi-square and student’s t-tests were used for categorical and continuous variables. Results: A total of 247 patients were included (210 patients received etomidate, 37 patients received ketamine). Baseline characteristics were similar between the two groups. The primary outcome showed similar 7-day (71.9% vs. 70.3%; p=0.84) and 28-day (59.5% vs. 62.2%; p=0.76) survival rates for etomidate and ketamine. Need for vasopressor support within 24-hours of intubation was more frequently seen in patients receiving ketamine as compared to etomidate (64.8% vs. 75.7%; p=0.21). Ketamine recipients required more frequent fluid boluses (13.5% vs. 3.8%) in addition to vasopressor support and longer durations of concurrent steroids (1 day vs. 3 days; p=0.32). There was no difference in mechanical ventilation duration (median 3 days, p=0.82), however median ICU length of stay in days was higher for the etomidate group (6 vs. 5, p=0.26). The safety endpoint of adrenal insufficiency post-intubation occurred in only 6 patients in the etomidate group. Conclusions: This retrospective chart review comparing the utilization of etomidate versus ketamine for RSI found no statistically significant difference in 7-day all-cause mortality. Individual patient factors such as reason for intubation, comorbidities, and pre-intubation hemodynamic stability should guide which induction agent is chosen for RSI.