Venous malformations of the face and neck involve multiple anatomical spaces and encase critical neuromuscular structures, making surgical treatment difficult; high recurrence rates and high morbidity are well documented. The purpose of this study was to evaluate the clinical curative effect of combination compartmentalisation and sclerotherapy for the treatment of massive venous malformations of the face and neck. Sixteen patients with massive venous malformations of the face and neck region (12 males and four females; mean age: 14.9 years, range: 6-22 years) were treated with compartmentalisation using silk sutures followed by injections of 0.1 mg OK-432 and 8 mg pingyangmycin into each small compartment. The injections were performed every two weeks. All lesions received three to six treatments. All the patients had significant swelling and mild pain postoperatively for a period of one to two weeks with no major complications. One patient had transient facial paresis, which resolved spontaneously within two weeks. The follow-up period ranged from three to 14 months (median: 7.1 months). The treatments resulted in the following: four of the lesions were completely involuted, six were mostly involuted, five were partially involuted, and one experienced a small involution. All of the patients had normal liver and kidney functions and normal lung fields on chest X-ray. Compartmentalisation followed by injection of OK-432 and pingyangmycin into each compartment provided a simple, safe, and reliable alternative treatment for massive venous malformations of the face and neck.