Airway obstruction and feeding difficulties vary among patients with Pierre Robin sequence (PRS). Treatment is challenging and the appropriate management may not be readily identified, leading to delay in securing the airway. A retrospective review of 90 children with PRS was done to identify subgroups at a higher risk of developing severe airway obstruction using oxygen and apnea monitoring, sleep studies, and response to treatment. Patients with isolated PRS (group I, 27 patients) and Stickler syndrome (group II, 32 patients) do not suffer from debilitating airway and feeding difficulties when compared to those with unique syndromes (group III, 16 patients) and recognized named syndromes (group IV, 15 patients). Feeding difficulties were universal with the severity proportional to airway obstruction. Aggressive intervention should be considered early in group III and IV patients.