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Background: Migraine headaches are a common reason for pediatric emergency department (ED) visits. Small studies suggest the potential efficacy of sub-anesthetic doses of propofol for migraine with a favorable side effect profile and potentially decreased length of stay (LOS).Objective: The objective of this study was to compare the efficacy of low-dose propofol (LDP) to standard therapy (ST) in pediatric migraine treatment.Methods: We conducted a prospective, pragmatic randomized controlled trial from April 2014 through June 2016 in the ED at two pediatric hospitals. Patients aged 7-19 years were eligible if they were diagnosed with migraine by the emergency physician and had a presenting visual analog pain score (VAS) of 6-10. Primary outcome was the percent of pain reduction. Secondary outcomes were ED LOS, 24-h rebound headache, return visits to the ED, and adverse reactions.Results: Seventy-four patients were enrolled, but 8 were excluded, leaving 66 patients in the final analysis (36 ST, 30 LDP). Pain reduction was 59% for ST and 51% for LDP (p = 0.34) with 72.2% vs. 73.3% achieving a VAS ≤ 4 with initial therapy (p = 0.92). There was a nonsignificant trend toward shorter median LOS from drug administration to final disposition favoring propofol (79 min vs. 111 min; p = 0.09). Rebound headache was significantly more common in the ST vs. LDP group (66.7% vs. 25.0%; p = 0.01).Conclusions: LDP did not achieve better pain reduction than ST, however, LDP was associated with significantly fewer rebound headaches and a nonsignificant trend toward shorter median LOS from drug administration to disposition. [ABSTRACT FROM AUTHOR]