BACKGROUND Multiple reports have demonstrated the efficacy of the transnasal endoscopic repair of cerebrospinal fluid (CSF) leaks of the anterior cranial base. The literature, however, lacks a comprehensive clinical study specifically addressing the transnasal endoscopic repair of CSF leaks of the sphenoid sinus. OBJECTIVE To ascertain the factors that significantly affect the surgical outcome after transnasal endoscopic repair of CSF leaks of the sphenoid sinus. METHODS We retrospectively reviewed the medical records of all patients who underwent an endoscopic transnasal repair of CSF leaks of the sphenoid sinus at our teaching hospitals. RESULTS Twenty-four patients with CSF leaks of the sphenoid sinuses that were repaired by the transnasal endoscopic approach were included in our study. Causes of the CSF leaks included trauma, surgery, neoplasms, and idiopathic causes. Obliteration was the most common technique used to repair the CSF fistulas (used in 15 [58%] of 26 procedures). Grafting materials included banked pericardium, mucosa, turbinate bone, and mucoperichondrium placed by underlay or onlay grafting or abdominal fat used to obliterate the sphenoid sinus. Twenty-two patients were successfully treated on the first attempt. A persistent leak in 2 patients with previously unrecognized high-pressure hydrocephalus was repaired during a second endoscopic surgery, quickly followed by ventriculoperitoneal shunting. CONCLUSIONS Assuming an adequate repair, other factors such as the cause, the size of the defect, the technique and material used to repair the defect, and perioperative management do not affect the surgical outcome significantly. Untreated high-pressure hydrocephalus can lead to a recurrence or persistence of the leaks and should be suspected in patients with posttraumatic, idiopathic, or recurrent CSF leaks.