The aim of this study was to develop an effective single intraoral, minimally invasive technique to reduce the enlarged tongue base in children with obstructive macroglossia. We present the anatomic dissection of fresh cadavers and a representative case series of children who underwent submucosal minimally invasive lingual excision (SMILE) with a plasma-mediated radiofrequency device (coblation) under intraoral ultrasonic and endoscopic guidance. Multiple anatomic dissections determined the relative location of the hypoglossal nerve and lingual neurovascular bundle in relation to removable tongue base musculature. A pediatric case series demonstrates the straightforward SMILE technique. Laboratory anatomic dissection and clinical lingual ultrasonography revealed the surgical safety borders for SMILE. The surgical safety and efficacy of SMILE is demonstrated by preoperative and postoperative clinical examinations and polysomnograms in children with obstructive macroglossia (such as Beckwith-Wiedemann and Down syndromes and tongue vascular malformation). Coblation submucosally removes excessive tongue base tissue through a small anterior tongue incision. SMILE was performed without excessive pain, bleeding, edema, infection, or tongue dysfunction. SMILE is an effective novel operation that incorporates coblation with ultrasonography and endoscopic guidance for children who need tongue base reduction. Anatomic dissection and clinical cases demonstrate the potential for aggressive yet relatively safe tissue removal by this minimally invasive technique. SMILE also has significant potential for adults with obstructive sleep apnea due to a large tongue base.