Although postoperative seizure is an acknowledged risk following transcranial surgery, the incidence of seizure after removal of intradural pathology via an expanded endoscopic endonasal approach is not well defined. The current study was performed to systematically review the risk of seizure in patients undergoing endoscopic endonasal skull base (EESB) surgery. Embase (1980 to 9 March 2012) and Medline (1950 to 9 March 2012) were searched using a search strategy designed to include any studies that report the perioperative outcomes following EESB surgery. Outcomes of patients undergoing a simple closure of cerebrospinal fluid fistulae or encephaloceles and transellar approaches for pituitary or intrasellar lesions were excluded because this review is focused on large skull base defects. A title search selected those articles relevant to clinical series on expanded endoscopic approaches. A subsequent search of abstracts selected for manuscripts of any report that documented the presence or absence of postoperative seizure. A total of 2234 manuscripts were selected initially and full text analysis produced 67 studies with extractable data regarding the perioperative outcomes for EESB surgery. Of these manuscripts, seven reported the incidence of seizure following EESB procedures. Two of these studies were excluded due to duplication of authorship and institutional data. The overall risk of postoperative seizure following EESB surgery was estimated at 1.1% (six of 530). Subgroup analyses of data revealed that the risk of seizure following an endoscopic endonasal to the anterior cranial base was 2.3% (one patient of 43). For a posterior cranial base approach, the risk of seizure was indeterminate due to deficiency of reporting in the current literature. We concluded that the risk of seizure following an EESB procedure appears to be low (1%). However, the lack of reporting on the incidence of seizures or the use of antiepileptic prophylaxis following EESB procedure is a key limitation. Future EESB studies will need to include seizure as an outcome to accurately define this risk.