22 patients scheduled for spinal decompression were randomized to receive either an S-ketamine intranasal spray or intravenous morphine PCA for postoperative pain. The purpose of the study was to determine the effects of and evaluate noninferiority of S-ketamine spray combined with a midazolam intranasal spray, when compared to morphine PCA, on pain, bolus demand and delivery, complications, and 5D-ABZ scores. The S-ketamine spray did not meet the noninferiority margin at 24 hours. However, there were no significant differences between groups in pain levels at 1, 2, 4, 24, 48, or 72 hours postoperatively. The results additionally indicated that patients in the morphine group experienced significantly more auditory hallucinations. There was no significant difference between groups in bolus demand or delivery, or in the incidence of complications.