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Abscess incision and drainage (I&D) are painful and distressing procedures in children. Intranasal (IN) fentanyl is an effective analgesic for reducing symptomatic pain associated with fractures and burns but has not been studied for reducing procedural pain during abscess I&D. Our objective was to compare the analgesic efficacy of IN fentanyl with intravenous (IV) morphine for abscess I&D in children.We performed a randomized noninferiority trial in children aged 4 to 18 years undergoing abscess I&D in a pediatric emergency department. Patients received IN fentanyl (2 μg/kg; maximum, 100 μg) or IV morphine (0.1 mg/kg; maximum, 8 mg). The primary outcome, determined independently by blinded assessors, was the Observational Scale of Behavioral Distress-Revised (OSBD-R). The prestated margin of noninferiority (Δ) was 1.80. Secondary outcomes included self-reported pain, treatment failure, and patient and parental satisfaction.We enrolled 20 children (median age, 15.4 years), 10 in each group. The difference between total OSBD-R scores was −13.45 (95% confidence interval, −24.24 to −2.67), favoring IN fentanyl.There was less self-reported pain in patients who received IN fentanyl immediately after the procedure. Four patients (40%) receiving IV morphine had treatment failures and required moderate sedation or had the procedure terminated. More patients who received IN fentanyl were satisfied with the analgesic administered compared with those who received IV morphine.In a small sample of children aged 4 to 18 years undergoing abscess I&D, IN fentanyl was noninferior, and potentially superior, to IV morphine for reducing procedural pain and distress.