Use of etomidate in severe sepsis and septic shock has been challenged in recent literature due to its link to adrenal insufficiency and suspected increased mortality. We hypothesized that etomidate does not contribute to mortality in this patient population. A retrospective chart review of 230 intubated, severe sepsis/septic shock patients at two university tertiary care referral centers was conducted for patients receiving treatment between 12/2001 and 10/2009. The primary endpoint was in-hospital mortality. Additional investigated variables included the use of corticosteroids, hospital and intensive care unit (ICU) length of stay, mechanical ventilation days and patient demographics. One hundred seventy-three patients received etomidate and fifty-seven patients received either no medication or an alternative drug. Use of etomidate in this patient cohort did not worsen mortality. Mortality in the etomidate group was 43. 9% (76/173). Mortality in the non-etomidate cohort was 45. 6% (26/57) (p = 0. 48). APACHE II scores were 22 ± 7. 2 and 23 ± 7. 1 for the etomidate group and the non-etomidate group, respectively, (p = 0. 36). There was no significant difference in mortality between etomidate and non-etomidate cohorts in this study. This large retrospective multi-center study further supports the safety of etomidate use in severe sepsis and septic shock.