OBJECTIVE We sought to investigate the anatomical relation of the intrasphenoid septations to the internal carotid artery (ICA). METHODS Twenty-seven preoperative high-resolution computed tomography angiographic (CTA) scans with 1 mm of separation acquisition were examined. In addition, an endoscopic endonasal approach and high-resolution computed tomography were done on 27 fresh-frozen cadaveric heads. The number of intrasphenoid septa and their relation to the ICAs were analyzed endoscopically and radiologically. Complete and incomplete septations were included in the analysis. A total of 54 sphenoid sinuses were studied. RESULTS Out of 27 sphenoid sinuses radiologically studied from real patients, 23 (85%) and 11 (41%) had at least one or two septa, respectively, touching one of the ICA. Out of 27 sphenoid sinuses endoscopically examined from cadavers (excluding one conchal type), 24 (89%) had at least one septation inserted in the ICAs. Two or more septations were inserted in the carotid prominence in 48% of sphenoid sinuses. The radiological examination of the anatomical specimens revealed similar results, with discrepancy in just one case (1/27) where it did not identify an incomplete septation inserting at ICA. No significant differences were found between the groups. From a total of 54 sphenoid sinuses studied, 47 (87%) had at least one septum related to the ICA, and only 13% presented a typical isolated midline septation. CONCLUSIONS As demonstrated both radiographically and endoscopically, most intrasphenoidal septa insert at the parasellar or paraclival carotid prominence. As such, extreme care should be taken when identifying and removing these septations intraoperatively.