Objective There has been increased interest in the use of low‐dose ketamine (LDK) as an alternative analgesic for the management of acute pain in the emergency department (ED). The objective of this systematic review was to compare the analgesic effectiveness and safety profile of LDK and morphine for acute pain management in the ED. Methods Electronic searches of Medline and EMBASE were conducted and reference lists were hand‐searched. Randomized controlled trials (RCTs) comparing LDK to morphine for acute pain control in the ED were included. Two reviewers independently screened abstracts, assessed quality of the studies, and extracted data. Data were pooled using random‐effects models and reported as mean differences and risk ratios (RRs) with 95% confidence intervals (CIs). We used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty of the evidence. Results Eight RCTs were included with a total of 1,191 patients (LDK = 598, morphine = 593). There was no significant difference in reported mean pain scores between LDK and morphine within the first 60 minutes after analgesia administration and a slight difference in pain scores favoring morphine at 60 to 120 minutes. The need for rescue medication was also similar between groups (RR = 1.26, 95% CI = 0.50 to 3.16), as was the proportion of patients who experienced nausea (RR = 0.97, 95% CI = 0.63 to 1.49) and hypoxia (RR = 0.38, 95% CI = 0.10 to 1.41). All outcomes were judged to have low certainty in the evidence. Conclusion Low‐dose ketamine and morphine had similar analgesic effectiveness within 60 minutes of administration with comparable safety profiles, suggesting that LDK is an effective alternative analgesic for acute pain control in the ED.