BACKGROUND: The prescribing of opioids to patients for postoperative pain can lead to persistent opioid use. This review investigated the effectiveness of interventions aimed at reducing opioid use in patients after orthopaedic surgery. METHODS: Electronic databases were searched from inception to November 2023. We included randomised controlled trials investigating interventions aimed at reducing opioid use after orthopaedic surgery. Two reviewers conducted the screening and data extraction and assessed the risk of bias (Cochrane Risk of Bias tool) and certainty of evidence (GRADE). The primary outcome was the mean daily dose of opioid analgesic medications in the medium term (1-3 months after randomisation). Results were pooled in a meta-analysis using a random-effects model where appropriate (e.g. I RESULTS: The search yielded 17,471 records, of which 39 trials were included. High heterogeneity meant that most comparisons could not be pooled. The mean daily dose was lower with multimodal analgesia interventions than with placebo/no intervention/usual care or active control in the medium term. No between-group differences were found between other pharmacological or non-pharmacological interventions and either placebo/no intervention/usual care or active control at the medium-term time point. The certainty of evidence ranged from low to moderate. CONCLUSIONS: Multimodal analgesic interventions may reduce opioid use compared with placebo/no intervention/usual care or active control in the medium term. However, the high heterogeneity and low certainty of evidence means it is uncertain which interventions are effective in reducing opioid use after orthopaedic surgery.