Postoperative macroglossia is a very rare complication associated with neurosurgical procedures. There have only been 16 cases reported in the literature. With regard to spine surgery, however, only two cases have been reported. The first report was a case where the complication of postoperative macroglossia occurred during occipitocervical spine surgery in a sitting position. In this second documented incident, we report a case of massive macroglossia, in a 44-year-old man, following posterior craniocervical fixation and fusion surgery performed in a sitting position. The patient had Klippel-Feil syndrome with basilar invagination preoperatively. Postoperative macroglossia was treated by partial glossectomy, because medical management (anti-edema therapy) failed. This complication is a life-threatening complication and must be treated promptly. Diverse etiologic mechanisms are discussed along with preventive and therapeutic measures.