Introduction: Intranasal dexmedetomidine (IND) is an emerging agent for procedural distress in children. However, studies to date have been limited by small samples and imprecise estimates of effect size. We sought to summarize the evidence on the effectiveness of IND for procedures associated with distress in children. Methods: We performed electronic searches of MEDLINE (1946-2018), EMBASE (1980-2018), Google Scholar (2018), CINAHL (1981-2018), Cochrane Central Register of Controlled Trials (2018), 6 clinical trials registries and conference proceedings (2010-2018). Title searches, data abstraction, and risk of bias assessments were performed in duplicate. We included all published and unpublished, randomized and quasi-randomized trials of IND for procedures in children younger than 19 years of age without language restriction. The methodological quality of studies was evaluated using the Cochrane Collaboration's Risk of Bias tool. The primary outcome was the proportion of participants that were deemed to be adequately sedated for the procedure. Results: Of 661 studies, 18 met inclusion criteria. Trials involved 2128 participants, age 1 month - 14 years (836, 39.3% females), who received IND 1 - 4 mcg/kg either by drops (n = 12), atomizer (n = 4), or both (n = 2). 12 trials were eligible for meta-analysis. 13 trials used validated instruments to assess sedation. All studies except one were associated with low or moderate risk of bias. For painful procedures (IV insertion; laceration repair; dental extraction), the pooled OR (95% CI) for adequate sedation and need for additional analgesia was non-significant [1.19 (0.53, 2.65)] and [2.16 (0.62, 7.49)], respectively (n = 5). For non-painful procedures (diagnostic imaging), the corresponding pooled OR (95% CI) favored IND [3.04 (1.58, 5.82)] and [4.44 (2.11, 9.35)], respectively (n = 7). Time to onset and duration of sedation ranged from 13-31 minutes and 41-91.5 minutes, respectively. For adverse effects, the pooled OR (95% CI) was not significantly different between IND and comparators [0.58 (0.22, 1.55] and there were no serious adverse events. Conclusion: IND at doses 1 to 4 mcg/kg are safe and adequately sedate children undergoing non-painful procedures, although the ease of administration must be weighed against the risk of prolonged sedation. Additional trials with larger sample sizes and greater methodologic rigor are needed for painful emergency department procedures such as laceration repair and IV insertion.