© 2016 by the Society for Academic Emergency Medicine Objective: Intranasal (IN) midazolam is a commonly prescribed medication for pediatric sedation and anxiolysis. One of its most frequently encountered adverse effects is discomfort with administration. While it has been proposed that premedicating with lidocaine reduces this undesirable consequence, this combination has not been thoroughly researched. The objective of our study was to assess whether topical lidocaine lessens the discomfort associated with IN midazolam administration. Methods: This was a double-blind, randomized, placebo-controlled trial performed in an urban, academic pediatric emergency department. Children 6–12 years of age who were receiving IN midazolam for procedural sedation received either 4% lidocaine or 0.9% saline (placebo) via mucosal atomizer. Subjects were subsequently given IN midazolam in a similar fashion and then rated their discomfort using the Wong-Baker FACES Pain Rating Scale (WBS). The primary endpoint of WBS score was analyzed with a two-tailed Mann-Whitney U-test, with p < 0.05 considered statistically significant. Results: Seventy-seven patients were enrolled over a consecutive 8-month period. One child was excluded from analysis due to a discrepancy in recording the drug identification number. Study groups were similar in regard to demographic information and indication for sedation. Subjects who received IN lidocaine reported less discomfort with IN midazolam administration (median WBS = 3, interquartile range [IQR] = 0–6) than those who received placebo (median WBS = 8, IQR = 2–9; p = 0.006). Conclusions: Premedication with topical lidocaine reduces the discomfort associated with administration of IN midazolam (ClinicalTrials.gov, NCT02396537).