Ninety elderly patients with lumbar spinal stenosis were randomized to receive high-dose esketamine (HS) (n=30), low-dose esketamine (LS) (n=30), or saline (control, C) (n=30) during total laminectomy and interbody fusion surgery. The primary outcome was the cumulative perioperative dose of sufentanil. Secondary outcomes included pain scores (VAS) at rest and during movement, serum inflammatory biomarkers (TNF-α, IL-1β, IL-6, IL-10), intraoperative hemodynamic stability, anesthetic requirements, adverse effects, and time to discharge. Outcomes were assessed preoperatively, and on postoperative days 1, 3, and 7. Overall, the results of the study revealed significantly lower perioperative sufentanil use, reduced inflammatory marker levels, better hemodynamic stability, and faster recovery in the HS and LS groups, with the HS group showing the most pronounced benefit. These findings suggest that low-dose esketamine, particularly at 0.2 mg/kg induction and 0.25 mg/kg/h infusion, improves analgesia and safety in elderly spinal surgery patients.