Objective <p>Children undergoing interventional treatment for vascular malformations (VMs) can easily develop perioperative atelectasis. High-flow nasal cannula (HFNC) oxygen therapy shows the potential to reduce perioperative atelectasis. The aim of our study was to explore the potential efficacy of HFNC oxygen therapy for reducing the incidence of perioperative atelectasis in Pediatric interventional treatment for vascular malformations.</p> Methods <p>This study was a prospective randomized controlled trial with patient-blinded structure. A total of 81 pediatric patients scheduled for interventional sclerotherapy for VMs were randomly divided into three groups: the mask oxygenation group (Group M) (<i>n</i> = 27), the endotracheal intubation group (Group T) (<i>n</i> = 27), and the HFNC group (Group H) (<i>n</i> = 27). The incidence of atelectasis was assessed at T₁ (at the end of surgery) and T₂ (upon discharge from the PACU).Other intraoperative and postoperative outcomes were also evaluated.</p> Results <p>A total of 80 pediatric surgical patients were included (26 patients in Group M, 27 patients in Group T, and 27 patients in Group H). Primary outcome was at T₂, significant atelectasis was observed in 17, 24, and 24 pediatric patients in Groups H, M, and T, respectively (63% vs. 88.9% vs. 92.3%; <i>P</i> = 0.011). The secondary outcomes were the awakening time, PAED score, incidence of agitation during awakening, and incidence of postoperative nausea and vomiting in Group M and Group H were significantly lower than those in Group T (<i>P</i> &lt; 0.05).</p> Conclusion <p>In summary, the use of transnasal high-flow oxygen therapy (HFNC) during DSA-guided interventional therapy for vascular malformations can reduce postoperative lung ultrasound scores (LUS) and the incidence of atelectasis in pediatric patients. General anesthesia with endotracheal intubation requires more anesthetic drugs, which may induce adverse reactions such as postoperative nausea, vomiting, and agitation in children, whereas the likelihood of such complications is reduced in children receiving HFNC. For pediatric patients at high risk of postoperative pulmonary complications, further research is needed to determine whether transnasal high-flow oxygen therapy during anesthesia maintenance can reduce the long-term risk of pulmonary complications.</p> Trial registration <p>Chinese Clinical Trial Registration number: ChiCTR2300078634.</p>