Background: 22q11.2 deletion syndrome (22q11.2DS) is a chromosomal disorder with a multisystem set of symptoms varying in clinical expression. Patients are at increased risk of airway anomalies, being partial laryngeal atresia (PLA) one of the most common. Surgical management of the airway secondary to PLA varies according to the severity of the airway obstruction and comorbidities. This analysis aimed to assess these findings and surgical outcomes of patients with a 22q11.2DS who presented with PLA. Methods: Retrospective review of patients with 22q11.2 DS with a diagnosis of PLA between 2009 and 2020. The patient’s age, symptoms, associated clinical anomalies, microlaryngoscopy and bronchoscopy (MLB) findings, Cohen’s laryngeal atresia classification, surgical technique and the need for tracheostomy, and degree of dysphagia, were evaluated. Results: Ten patients aged between 4 days and 17 months were identified, 8 underwent surgery to treat atresia. The main presenting symptoms were stridor (75%), dysphonia (62%), and dysphagia (85%). Clinical comorbidities were cardiac pathology (75%), craniofacial anomalies (50%), global development delay (62.5%), palate defects (75%), and immunodeficiency (50%). Classification: 33% Cohen type I, 11% type II and 56% type III. Three had synchronous airway anomalies. Surgical procedures included endoscopic web division (n=3), laryngotracheal reconstruction (LTR) with anterior cartilage graft (n=4), and slide thyro-crico-tracheoplasty (n=1). Three patients required a peri-operative tracheostomy. At the last MLB, all patients were sized with an age-appropriate airway and were free of tracheostomy. Conclusions: Laryngeal atresia is a common abnormality in 22q11.2DS and a careful endoscopic airway evaluation should be mandatory in case of stridor. Dysphonia and dysphagia are common in this group. While children with mild laryngeal obstruction are successfully treated with an endoscopic procedure, patients with severe obstruction will require open airway reconstruction. LTR should be considered at a young age among these patients to avoid long term tracheostomy complications.