Background: Methohexital has been used for procedural sedation in the emergency department, but its use for endotracheal intubation in intensive care units has not been studied. Objective: To compare methohexital with etomidate with respect to their effectiveness and safety of use for endotracheal intubation in the intensive care unit. Methods: Retrospective, observational, single-center cohort study of consecutive patients admitted between December 2006 and August 2007 to a medical intensive care unit in a tertiary-care hospital. Results: Twenty-three patients who received methohexital and 23 who received etomidate for endotracheal intubation were included. The 2 groups differed in age (mean [SD], 55  vs 64  years, P =.03) but not in baseline demographics or illness severity scores. Mean (SD) doses given were 1 (0.2) mg/kg for methohexital and 0.2 (0.1) mg/kg for etomidate. Use of midazolam, fentanyl, and succinylcholine was similar between the groups. Rates of successful intubation after 1 attempt (78% vs 83%), time to successful intubation (mean, 5.9 vs 4 minutes), and number of intubation attempts (mean, 1.5 vs 1.2) also were similar. Change in hemodynamics (delta systolic blood pressure), vasopressor requirements, and amount of fluid resuscitation (normal saline) did not differ significantly between the groups. Conclusions: Rates of successful intubation are similar with etomidate and methohexital. Methohexital provides adequate sedation and could be an alternative to etomidate, although both agents were often associated with development of hypotension. Prospective studies are needed to establish the safety of methohexital use in intensive care patients. © 2010 American Association of Critical-Care Nurses.