Purpose <p>We aimed to evaluate the effects of intravenous dexmedetomidine (DEX) on perioperative opioid requirements, and secondarily on perioperative respiratory adverse events (PRAE), emergence delirium (ED), and postoperative nausea and vomiting in pediatric patients undergoing tonsillectomy.</p> Methods <p>We conducted a systematic review with meta-analysis, searching seven databases up to 7 May 2024. We included randomized controlled trials of patients aged 18&#xa0;yr or younger undergoing tonsillectomy, comparing intravenous DEX and opioids with opioids. Our primary outcome was perioperative opioid requirements, expressed as oral morphine equivalents (OME). The secondary outcomes included the incidences of perioperative respiratory adverse events (PRAE), emergence delirium (ED), and postoperative nausea and vomiting (PONV), We used the Cochrane Risk of Bias 2 tool and assessed the certainty of the evidence with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). We used a pairwise random effects model to compute the risk ratios (RRs) or mean differences (MDs) with 95% confidence intervals (CIs) of the effects of DEX on each outcome. To explore dose-dependent effects of DEX, we used a random effects meta-regression model.</p> Results <p>We included 16 trials in our systematic review, of which we analyzed 7 for opioid requirements, 4 for PRAE, 3 for ED, and 12 for PONV. Dexmedetomidine was associated with lower perioperative opioid requirements (MD, −0.25&#xa0;mg·kg⁻¹ OME; 95% CI, −0.36 to −0.13; moderate certainty), equivalent to a 40% relative reduction of perioperative OME, and a lower likelihood of ED (RR, 0.24; 95% CI, 0.08 to 0.71; moderate certainty). Despite DEX not having a dose-dependent effect on OME, the RR of ED decreased 87% for each 0.5&#xa0;µg·kg⁻¹ increment in DEX dose. Dexmedetomidine did not reduce the incidence of sustained or severe cough as a part of PRAE, but it reduced PONV (RR, 0.48; 95% CI, 0.35 to 0.66; <i>I</i>² = 0%; low certainty).</p> Conclusion <p>Dexmedetomidine may improve the perioperative course of children undergoing tonsillectomy by decreasing perioperative opioid requirements and dose-dependently lowering the incidence of ED. Limitations of the present systematic review with meta-analysis include an inconsistent definition of PRAE in trials and heterogeneity due to variability of observed effect sizes.</p> Study registration <p>PROSPERO (<a href="https://www.crd.york.ac.uk/PROSPERO/view/CRD42023392579">CRD42023392579</a>); first submitted 1 July 2023.</p>