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Patients undergoing spinal fusion surgery often experience severe pain during the first three postoperative days. The aim of this parallel-group randomized trial was to assess the effect of the long-duration opioid methadone on postoperative analgesic requirements, pain scores, and patient satisfaction after complex spine surgery.One hundred twenty patients were randomized to receive either methadone 0.2 mg/kg at the start of surgery or hydromorphone 2 mg at surgical closure. Anesthetic care was standardized, and clinicians were blinded to group assignment. The primary outcome was intravenous hydromorphone consumption on postoperative day 1. Pain scores and satisfaction with pain management were measured at postanesthesia care unit admission, 1 and 2 h postadmission, and on the mornings and afternoons of postoperative days 1 to 3.One hundred fifteen patients were included in the analysis. Median hydromorphone use was reduced in the methadone group not only on postoperative day 1 (4.56 vs. 9.90 mg) but also on postoperative days 2 (0.60 vs. 3.15 mg) and 3 (0 vs. 0.4 mg; all P< 0.001). Pain scores at rest, with movement, and with coughing were less in the methadone group at 21 of 27 assessments (all P = 0.001 to < 0.0001). Overall satisfaction with pain management was higher in the methadone group than in the hydromorphone group until the morning of postoperative day 3 (all P = 0.001 to < 0.0001).Intraoperative methadone administration reduced postoperative opioid requirements, decreased pain scores, and improved patient satisfaction with pain management.