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Background: Deaths related to opioid overdoses are increasing in North America, with the emergency department being identified as a potential contributor toward this epidemic. Our goal was to determine whether a departmental guideline for the prescribing of restricted medications resulted in a reduction in opioids prescribed in a Canadian setting, with a secondary objective of determining the impact on local overdose frequency., Methods: We conducted a retrospective analysis of the prescribing habits of emergency department physicians in 3 hospitals in the Saskatoon Health Region, Saskatchewan, before (Nov. 1, 2015, to Apr. 30, 2016) and after (Nov. 1, 2016, to Apr. 30, 2017) implementation of a guideline in September 2016 for the prescribing of restricted medications. We quantified opioids prescribed per hour worked and per patient seen. We performed Student paired 2-tailed t tests for both individual drug formulations and the combined total morphine equivalents., Results: Thirty-two emergency department physicians were included. We found a decrease of 31.1% in opioids prescribed, from 10.36 morphine milligram equivalents (MME) per patient seen to 7.14 MME per patient seen (absolute change -3.22 MME, 95% confidence interval -4.81 to -1.63 MME). Over the same period, we found no change in prehospital naloxone use and a modest increase in the amount of naloxone dispensed by emergency department pharmacies. There was no decrease in the number of overdoses after guideline implementation., Interpretation: Implementation of a guideline for the prescribing of restricted medications in a Canadian emergency department setting was associated with a decrease in the quantity of opioids prescribed but not in the number of overdoses. This finding suggests that the emergency department is unlikely the source of opioids used in acute overdose, although emergency department opioid prescriptions cannot be ruled out as a risk factor for opioid use disorder., Competing Interests: Competing interests: Luke Terrett is the creator of the Saskatoon Health Region emergency department guideline for the prescribing of restricted medications. He received no additional funding for his role in the development and implementation of the guideline. No other competing interests were declared., (© 2021 Joule Inc. or its licensors.)