Objective: We compared the mortality rate in patients administered a single dose of etomidate or S-ketamine for tracheal intubation during their stay on the intensive care unit. Methods: A single centre prospective open-label study was performed. Intensive care patients with a diversity of diagnoses were included. For tracheal intubation, etomidate or S-ketamine were used; the primary endpoint was 28-day mortality. Length of stay, the usage of norepinephrine, and cortisol concentrations were secondary end points. Results: A total of 322 patients with a mixture of diagnoses were initially included. After exclusions, 301 patients participated; 161 patients in the etomidate group and 140 patients in the S-ketamine group were analysed. The 28-day mortality of the etomidate patients was 38% and of the S-ketamine patients 39% (p=0.998). The length of stay was 16 days in the etomidate group and 19 days (p=0.318) in the S-ketamine group; the time of norepinephrine administration was 26 versus 29 hours (p=0.389) respectively. 24 and 48 hrs after administration of either drug, the cortisol levels had significantly decreased; there was no statistical difference between the etomidate and S-ketamine patients. Conclusion: In contrast with a currently held opinion, the present study showed that the 28-day mortality after a single dose of etomidate or S-ketamine, administered to patients for tracheal intubation while on the intensive care did not differ.