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Background: Development of a widely accepted standardised analgesic pathway for adult spine surgery has been hampered by the lack of quantitative analysis. We conducted a systematic review and network meta-analysis (NMA) to compare, rank, and grade all pharmacological and regional interventions used in adult spine surgery. Methods: A systematic search was performed in January 2021. We performed double study screening, selection, and data extraction. The co-primary outcomes were cumulative morphine consumption (mg) and visual analogue pain score (range 0e10) at postoperative 24 h. An NMA was performed using the Bayesian approach (random effects model). We also ranked and graded all analgesic interventions using the Grading of Recommendations Assessment, Development and Evaluation approach for NMA. Results: We screened 5908 studies and included 86 randomised controlled studies, which comprised 6284 participants. Of 20 pharmacological and 10 regional interventions, the most effective intervention was triple-drug therapy, consisting of paracetamol, nonsteroidal anti-inflammatory drugs, and adjunct. The pooled mean reduction in morphine consumption and pain score at postoperative 24 h were e26 (95% credible interval [CrI]: e39 to e12) mg and e2.3 (95% CrI: e3.1 to e1.4), respectively. Double-drug therapy was less effective, but showed moderate morphine reduction in a range of e15 to e17 mg and pain score reduction in a range of e1 to e1.6. Single-agent interventions were largely ineffective. Conclusions: Triple-drug therapy is the most effective pain intervention in adult spine surgery with moderate-to-high certainty of evidence. We have also identified a graded analgesic effect, in which analgesic efficacy increased with the number of multimodal drugs used. Systematic review registration: PROSPERO (CRD42020171326).

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