Background: Recent literature shows that there can be a function for ketamine in managing depression, bipolar disorder, posttraumatic stress sickness, suicidal ideation, refractory continual headache, reputation epilepticus, and acute agitation in the ED. Aim: This work aims to determine the efficacy and safety of Ketamine versus standard Opioid treatment for acute pain patients in the emergency setting. Materials and Methods: A systematic search was performed over different medical databases to identify Emergency Medicine studies, which studied the outcome of the Ketamine group versus the Opioid group of acute pain patients. Using the meta-analysis process, either with fixed or random-effects models, we conducted a meta-analysis on a numeric rating scale (NRS score), as a primary efficacy outcome, and on serious adverse effects (SAE rate), as a secondary safety outcome. Results: Eight studies were identified involving 796 patients, 394 in the Ketamine group, and 402 in the Opioid group. The meta-analysis process revealed a non-significant difference in the mean NRS score and SAE rate in the Ketamine group compared to the Opioid group (p > 0.05). Our results indicating that ketamine can be considered as an alternative to opioids for short-term pain control. Conclusion: To conclude, Ketamine is non-inferior to morphine for the control of acute pain, indicating that ketamine can be considered as an alternative to opioids for ED short-term pain control.