ObjectiveTo evaluate the effectiveness of a subanaesthetic single-dose ketamine (SDK) as an adjunct to opioids for acute pain in emergency department (ED) settings.DesignSystematic review and meta-analysis.MethodsA systematic search was performed in MEDLINE, Embase, Scopus and Web of Science through March 2022. Randomised controlled trials (RCTs) that investigated SDK as an adjunct to opioids in adult patients for any painful condition in ED settings were selected. Two reviewers screened studies, extracted data and assessed study quality. Data were pooled using random-effects models. The primary outcome was mean pain intensity score measured at baseline, >0–15 min, >15–30 min, >30–45 min, 60 min, 90 min and 120 min. Secondary outcomes included need for rescue analgesia, adverse events and patient satisfaction. Results were reported as mean differences (MDs) and risk ratios. Statistical heterogeneity was calculated using theI²statistic.ResultsEight RCTs were included (n=903). Studies were judged to be at moderate to high risk of bias. Mean pain intensity scores were significantly lower 60 min after study drug administration favouring adjuvant SDK (MD −0.76; 95% CI −1.19 to −0.33), compared with opioids alone. There was no evidence of differences in mean pain intensity scores at any other time point. Patients who received adjuvant SDK were less likely to require rescue analgesia, no more likely to experience serious side effects and had higher satisfaction scores, compared with opioids alone.ConclusionsAvailable evidence suggests adjuvant SDK can have an effect on lowering pain intensity scores. Although reduction of pain scores was not clinically significant, the combination of reduced pain intensity and reduced opioid requirements suggest the results could be clinically important and support the potential utility of SDK as an adjunct to opioids to treat acute pain in adult ED patients. However, current evidence is limited and higher quality RCTs are needed.PROSPERO registration numberCRD42021276708.