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Traditional routes for administration of pain medications include oral (PO), intravenous (IV), or intramuscular routes (IM). When these routes are not feasible, the intranasal (IN) route may be considered. The objectives of this evidence-based review were: to review the literature which compared the safety and efficacy of IN analgesia to traditional routes and to determine if IN analgesia should be considered over traditional routes for acute pain control in the ED.The MEDLINE and EMBASE databases from July 1970 to July 2017 were searched. Randomized controlled trials (RCT) that evaluated the use of IN analgesia for acute pain in the ED were included. Methodological quality of the trials was assessed using the Grading of Recommendations Assessment, Development, and Evaluation criteria.Eleven randomized controlled trials (RCT) met the inclusion criteria. Four trials found significant reductions in pain scores, favoring IN analgesia. However, in all of the trials, pain relief was not sustained. Three trials reported superior pain reduction with comparators and three trials reported no statistical significance. One trial described effective pain relief with IN analgesia but did not provide data on statistical analysis.Eleven randomized controlled trials with various methodological flaws revealed conflicting conclusions. There is limited evidence to support the use of the IN analgesia over traditional routes for acute pain in the ED. The IN route may be a good alternative in scenarios where IV access is not feasible, patients are refusing injectable medications, or a fast onset of pain relief is needed.