BACKGROUND: Opioids are prescribed for postsurgical pain management, but a balance between achieving adequate pain control and minimising opioid-related harm is required. This study aimed to investigate the effectiveness of different opioid regimens, in daily dose or treatment duration, prescribed at surgical discharge. METHODS: A systematic search of MEDLINE, EMBASE, CENTRAL, and ICTRP was performed from inception to 12 January 2025. Randomised controlled trials (RCTs) and non-RCTs comparing different daily doses or treatment durations of opioid analgesics were included. All surgeries were included, except those related to cancer treatment or palliative care. Eligible populations were adults (≥ 18 years) or individuals classified as adults according to the criteria of the respective studies. Data were extracted at immediate-term (≤ 3 days), short-term (>
3 to ≤ 7 days), medium-term (>
7 to ≤ 30 days), and long-term (>
30 days). Data from RCTs were pooled using a random-effects model. Risk of bias was assessed. Certainty of evidence from RCTs was evaluated with Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). The primary outcome was pain intensity. Adverse events were also measured. RESULTS: A total of 8432 records were identified. In total, 12 RCTs with 7128 patients and 24 non-RCTs with 118,849 patients were included. Studies included orthopaedic, gynaecology and obstetric surgeries, ranging from minor to major procedures. Higher-doses of opioids were more effective than lower-doses in reducing immediate pain intensity (mean difference (MD) 4.36, 95% confidence interval (CI) 0.50-8.23, n = 364, three studies, I CONCLUSIONS: Higher-dose opioids provide a slight reduction in immediate post-discharge pain intensity but may lead to more adverse events. Longer durations of opioid treatment are probably not more effective in reducing pain than shorter treatment durations. Our findings suggest that clinicians may choose to prescribe lower doses of opioids or shorter durations of opioids without compromising pain control, even for major surgery.