Procedures to relieve airway obstruction in Pierre Robin sequence (PRS) include glossopexy, mandibular distraction, and tracheostomy. Previously, it has been suggested that the imbalance of the genioglossus insertion on the mandible could be responsible for the micrognathia, tongue elevation, and glossoptosis seen in PRS. We performed a retrospective study to determine the usefulness of subperiosteal release of the floor of the mouth in PRS with airway problems. Between 1991 and 2005, 14 consecutive patients with PRS were treated with subperiosteal release of the floor of the mouth performed at the British Columbia's Children's Hospital. There were 8 boys and 6 girls. Mean age at surgery was 15 weeks (range, 1-68 weeks). Postoperative follow-up ranged from 8 months to 13 years. Seven patients (4 boys and 3 girls) were successfully treated, and a tracheostomy was prevented. Fifty-five percent of the syndromic patients needed a tracheostomy, whereas 1 patient (33%) with isolated PRS needed a tracheostomy. The most common syndrome associated with PRS was Stickler syndrome. Five (72%) of the 7 patients who required a tracheostomy were boys. If conservative measures fail to relieve supraglottic airway obstruction seen in patients with PRS, a subperiosteal release of the floor of the mouth can be an effective intervention in certain patients. It is a simple intervention with few complications and little morbidity. More investigations are mandatory to precisely define patient characteristics ideal for this intervention.