Introduction: Ketamine is a popular sedative agent for painful procedures. It is not widely used at sub-dissociative analgesic doses in the emergency department (ED). We sought to determine the performance of low-dose ketamine (LDK) as an analgesic for acute pain management in adult patients in the ED. Methods: We systematically reviewed electronic databases (MEDLINE, EMBASE, AMED, CINAHL, PubMed and Cochrane database of systematic reviews), grey literature, conference proceedings and clinical trials registries. Two independent reviewers identified eligible studies using pre-determined criteria. We included peer-reviewed studies that used LDK (<1 mg/kg IV or <2mg/kg IM) in adult patients (>18 yo) requiring acute pain management for any condition in the ED. Our outcome measures included analgesic effect of LDK compared to any opioids, need for rescue analgesia, and neuropsychological adverse events. We assessed inter-rater agreement using kappa statistics, risk of bias using the Cochrane Collaboration’s Tool, and propose a treatment recommendation using GRADE. Heterogeneity among studies precluded meta-analysis. Results: We reviewed 1,408 studies and selected 44 for full review (kappa = 0.70). Thirty-three were excluded due to wrong patient population and non-analgesic use of ketamine. Eleven studies with 1,249 participants were included - six randomized control trials (RCTs) and five observational studies. All of which had an overall low risk of bias. There was extensive variation in the dose and route of LDK used (0.1 - 0.7 mg/kg SC/IV/IM), administration protocols, and use of adjunct analgesia. There is a lack of high quality data regarding the use of LDK as an analgesic agent in the ED. However, the current moderate quality data demonstrates a significant analgesic effect of LDK with occasional need for rescue analgesia and neuropsychological adverse events. Commonly reported neuropsychological adverse events included dizziness, dysphoria, and confusion, rarely agitation or hallucinations. All adverse events were self-limited or occasionally required benzodiazepines for resolution. Conclusion: Our GRADE evidence table identified moderate quality evidence from six RCTs supporting the analgesic effect of LDK for acute pain management in the ED when compared to using opioids alone.