Background: We aimed to explore the effect of intraoperative S-ketamine on analgesic consumption and pain one year after spine surgery in chronic opioid-dependent patients undergoing spinal fusion surgery. Methods: Single-centre, randomized, blinded trial of 147 patients. Intervention: Perioperative S-ketamine bolus 0.5 mg/kg followed by S-ketamine 0.25 mg kg −1 hr −1 infusion or placebo. Main outcomes: Analgesic use, pain (visual analogue scale 0–100 mm [VAS]) and labour market attachment one year after surgery assessed by written questionnaires. Results: Response rate was 67%. One year after surgery, the daily use of oral morphine equivalents was lower in the ketamine group versus the placebo group: 0 (0–20) mg versus 20 (0–62) mg, (p = 0.02), and fewer patients had a daily use of any analgesics in the ketamine group versus placebo group, 42% (95% CI 23–61) versus 74% (95% CI 58–87), (p = 0.04). Mobilization pain was lower in the ketamine group compared to the placebo group: Median difference 17 mm (95% CI −30 to −3), (p = 0.02). Pain at rest was lower in the ketamine group compared to the placebo group with median difference: 13 mm (95% CI −23 to −3), (p = 0.01). Further, labour market attachment was better in the ketamine group, (p = 0.02). Conclusion: Intraoperative ketamine may reduce analgesic use, pain, and improve labour market attachment one year after spine surgery in a chronic opioid-dependent population. Significance: This randomized clinical trial shows that intraoperative ketamine may reduce opioid use and pain and improve labour market attachment one year after spine surgery in an opioid-dependent population.