Purpose This study compared the incidence of clinical hypotension between ketamine and etomidate within a 24 hour period following endotracheal intubation. Materials and methods This single-center, retrospective propensity-matched cohort study included septic patients admitted to our medical intensive care unit who received either etomidate or ketamine for intubation. Clinical hypotension was defined as any one of the following: mean arterial pressure (MAP) decrease >40% compared to baseline and MAP 30% of the initial vasopressor dose. Results Patients were matched based on propensity scores determined by demographics and baseline characteristics. A total of 384 (200 etomidate and 184 ketamine) patients were included for analysis with 230 patients (115 in each group) matched. Clinical hypotension was less prevalent in patients who received ketamine as compared to etomidate [51.3% vs. 73% (odds ratio = 0.39, 95% confidence interval = 0.22-0.67, P = .001]. The etomidate group experienced significantly lower MAPs at time periods 6.1-12 hours (65.1 mmHg vs. 69.3 mmHg, P = .01) and 12.1-24 hours (63.9 mmHg vs. 68.4 mmHg, P = .003). Conclusions Ketamine was associated with a lower incidence of clinical hypotension within the 24 hour period following endotracheal intubation in septic patients.