Objective: This review was conducted to define the natural history of unoperated Beckwith-Wiedemann syndrome (BWS) macroglossia and the effect of tongue reduction surgery upon breathing, eating, speaking and dentoskeletal development in individuals having BWS. Design: This is a retrospective study of medical records. Setting: All patients were evaluated and treated in one of two Children's Hospitals by an ACPA approved Craniofacial Team. Patients/Participants: Medical records were reviewed of 526 individuals having a diagnosis of BWS and evaluated in-person by a single craniofacial surgeon between 1986 and 2014 in conjunction with a series of multi-disciplinary craniofacial team colleagues. 28 individuals were excluded having had multiple tongue reductions elsewhere. 498 individuals comprise the “pre tongue-reduction group”. The “post tongue-reduction group” consists of 391 individuals who underwent surgical tongue reduction by one surgeon using one technique between 1986 and 2014. Main Outcome Measures: The primary outcome measure was change in anterior dental occlusion following tongue reduction surgery. Tongue reduction surgery was performed on the assumption that it would improve dentoskeletal relationships. Secondary outcome measures were: breathing, feeding/swallowing, and speech. Results: A significant difference (p<0.001) over time between the two groups was found with less anterior occlusal abnormality in the tongue reduction group. Tongue reduction surgery had no mortality and minimal morbidity for breathing, feeding/swallowing, and speech and can ameliorate obstructive sleep apnea. Conclusions: Surgical tongue reduction for BWS macroglossia is recommended for the infant or child in primary dentition with a grossly abnormal anterior tooth/jaw relationship and/or obstructive sleep apnea.