<p>Aims: This study examines and summarizes the management outcomes over the past five years for sirolimus (rapamycin) treatment in patients with vascular malformations of the head and neck, focusing on its efficacy, side effects, and clinical outcomes. Methods: A retrospective analysis of six cases involving sirolimus treatment in patients with vascular malformations of the head and neck was performed in a tertiary academic medical institution. All patients were referred to the Ear, Nose, and Throat (ENT) clinic due to airway involvement. Results: Six patients, ranging in age from newborn to 49 years, were treated with sirolimus for vascular malformations causing upper airway obstruction. The most commonly used initial dose was 0.8 mg/m² per dose, titrated to achieve target blood levels of 10–15 ng/mL. Treatment durations ranged from 1 to 1.5 years. Most lesions demonstrated a reduction in size and improvement in clinical symptoms, particularly in the airway, resulting in significant improvement in quality of life. Conclusion: This study supports the use of sirolimus as a first-line treatment for vascular malformations, including in infants, when no contraindications are present. A multidisciplinary approach is essential to optimize management outcomes for this challenging group of patients.</p>