Methods: The study included 60 patients graded American Society of Anesthesiologists I and II and scheduled for thoracolumbar spine surgery involving >3 vertebral levels. The patients were divided into two groups: group KD (ketodex) and group F (fentanyl). The primary objective was to compare the postoperative analgesic requirements among the groups. The secondary objectives included a comparison of the intraoperative anesthetic requirements, postoperative pain scores, hemodynamic parameters, side effects of the study drugs, and the duration of post-anesthesia care unit stay of both the groups. Results: Ketodex use prolonged the mean time to first rescue analgesia (22.00±2.30 hours vs. 11.69±3.02 hours, p <0.001) and reduced the requirement of rescue analgesics in the first 24 hours postoperatively compared to fentanyl use (70.00±8.16 μg vs. 113.31±36.65 μg, p =0.03). The intraoperative requirement of desflurane was comparable between the groups (p >0.05). The postoperative pain scores were significantly lower in the group KD than in group F at most timepoints (p <0.05). Patients in group KD had a shorter post-anesthesia care unit stay than group F did (p <0.001). Conclusions Low-dose ketodex could be a safe substitute for fentanyl infusion when employed as an anesthetic adjuvant for patients undergoing thoracolumbar spine surgeries involving >3 vertebral levels to achieve prolonged analgesia without any opioidrelated side effects.