Objectives To evaluate the management of patients with large skull base defects (> 2 cm) and intracranial injury caused by powered endoscopic sinus surgery. Study design and setting All patients treated for postendoscopic sinus surgery skull base injury over a 4-year period were reviewed. Results Three patients with skull base defects greater than 2 cm in size and associated intracranial injury from powered ESS were identified. All patients presented with active cerebrospinal fluid leaks. CT scans showed intracranial injury and pathology reports revealed brain tissue removal. Using image-guided endoscopic techniques, all defects were addressed with multilayer repair. Closure was achieved in all patients on the first attempt, with an average follow-up of 27 months. Conclusions The use of powered instrumentation along the skull base can be dangerous and can result in extensive skull base defects with associated loss of dura and gray matter. Large ethmoid roof defects and significant intracranial injury, however, are not absolute contraindications to endoscopic repair.