Background/Objectives: Bleomycin electrosclerotherapy (BEST), which combines intralesional bleomycin administration with electroporation, enhances drug uptake and has shown efficacy in treating vascular malformations resistant to conventional therapies. While BEST is increasingly used in various anatomical sites, its application in the upper aerodigestive tract remains underexplored. This study evaluates the safety and effectiveness of BEST in managing slow-flow vascular malformations of the oral cavity, tongue, larynx, and hypopharynx. Methods: In this retrospective, multicenter study, 20 patients with symptomatic slow-flow vascular malformations of the upper aerodigestive tract were treated with BEST. Clinical and radiological assessments were used to evaluate the treatment response, categorized as “significantly reduced”, “reduced”, “stable disease”, or “lesion growth”. Postprocedural complications and functional outcomes were systematically recorded. Results: A total of 29 BEST sessions were performed. Lesions of the tongue (n = 8) and combined oral cavity and tongue (n = 6) showed the highest response rates, with significant symptom reduction in five out of eight and five out of six patients, respectively. Among isolated oral cavity lesions (n = 4), one out of four demonstrated a significant reduction. In contrast, laryngeal and hypopharyngeal lesions (n = 2) had limited response, with one case showing partial reduction and the other remaining stable. Severe complications, including bleeding and dyspnea requiring tracheostomy, limited further treatment in these locations. No systemic adverse events, such as pulmonary toxicity, were observed. Conclusions: BEST is effective for treating vascular malformations of the upper aerodigestive tract, particularly in the tongue and oral cavity, but presents significant risks in laryngeal and hypopharyngeal lesions. A multidisciplinary approach is required to optimize treatment protocols for these challenging locations.