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Prior to 2020, pain management in the Washtenaw/Livingston County Medical Control Authority (W/L MCA) Emergency Medical Service (EMS) system in Southeast Michigan was limited to morphine, fentanyl, ketorolac, and acetaminophen. Based on the increasing evidence describing its safety and efficacy, ketamine was added to local protocols for pain management. This study aimed to evaluate differences in pain management and adverse effects of ketamine and opioid administration. Data from pediatric patients who received ketamine or an opioid in the W/L MCA EMS system from October 2019 to March 2021 were analyzed. The primary outcome was the difference in pain score, and the secondary outcome was adverse effects observed after analgesic administration. The decrease in pain scores was greater among ketamine patients (mean: 5.2) compared to opioid patients (mean: 2.9), p  < 0.001. The prevalence of adverse effects was higher among patients in the ketamine group (28.6%) compared to patients in the opioid group (2.4%, p  < 0.001). Of 14 patients who received ketamine, one 17-year-old male experienced mild anxiety (7.1%), two teenage females experienced mild dissociation (14.3%), and one 20-year-old female experienced mild nausea (7.1%). Overall, ketamine is a safe and effective option compared to opioids for pediatric patients experiencing moderate to severe prehospital pain.