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Buprenorphine appears to have a ceiling effect on respiratory depression, but not analgesia in healthy young patients. However, the efficacy and side-effects of buprenorphine in the setting of acute pain are poorly characterized. The aim of this study was to characterize the analgesic efficacy and adverse effects of buprenorphine compared with morphine in the acute pain setting. A systematic review of five databases was performed. Randomised controlled trials (RCTs) comparing buprenorphine with morphine in acute pain management were included. Studies performed outside of the hospital setting were excluded. The a priori primary outcomes included pain, respiratory depression, and sedation. Secondary outcomes included requirement for rescue analgesia, time to rescue analgesia, nausea, vomiting, dizziness, hypotension, and pruritus. Twenty-eight RCTs with 2210 patients met the inclusion criteria. There was no difference in pain [visual analogue scale weighted mean difference (WMD)=−0.29; 95% confidence interval (CI)=−0.62 to 0.03; I2=99%; P=0.07], incidence of respiratory depression [odds ratio (OR)=2.07; 95% CI=0.78–5.51; I2=30%; P=0.14], or sedation (OR=1.44; 95% CI=0.76–2.74; I2=23%; P=0.26). There was only one secondary outcome with an overall significant difference; buprenorphine use was associated with significantly less pruritus (OR=0.31; 95% CI=0.12–0.84; I2=6%; P=0.02). Whilst a theoretical ceiling effect may exist with respect to buprenorphine and respiratory depression, in a clinical setting, it can still cause significant adverse effects on respiratory function. However, given that buprenorphine is an equally efficacious analgesic agent, it is a useful alternative opioid because of its ease of administration and reduced incidence of pruritus.