Methods: One hundred patients undergoing MISS were randomized into two groups. Patients in the nefopam group received 20 mg of intravenous nefopam diluted in 100 mL of normal saline intraoperatively, followed by 80 mg of nefopam diluted in 500 mL of normal saline, given as a continuous infusion postoperatively for 24 hours. The control group received an identical volume of normal saline. Postoperative pain was managed by patient-controlled analgesia in the form of intravenous morphine. Morphine consumption in the first 24 hours was recorded as a primary outcome. Secondary outcomes regarding ERAS were also collected. Results: There were no significant differences in either total morphine consumption or postoperative pain score in the first 24 hours postoperatively between patients receiving nefopam and the control group. Morphine consumption in patients receiving nefopam was 13.54±10.64 mg compared with 15.86±16.2 mg in the control group (p=0.41). Time to postanesthetic care unit discharge, times to first sitting and walking, length of hospital stay, as well as duration of Foley catheter use and time until drain removal were also similar. There were no serious adverse effects of nefopam compared with normal saline. Conclusions Nefopam did not significantly reduce opioid consumption or postoperative pain score. Adding nefopam as part of multimodal analgesia did not show beneficial effects for enhancing recovery after spine surgery.