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Non-vascularized multilayer fascial closure technique (NMFCT) can be used instead of nasoseptal flap reconstruction for dural repair in endoscopic transnasal surgery (ETS); however, due to the lack of blood supply, its long-term durability and possible limitations need to be clarified. This was a retrospective study on patients who underwent ETS with intraoperative cerebrospinal fluid (CSF) leakage. We assessed the postoperative and delayed CSF leakage rates and the associated risk factors. Among 200 ETSs with intraoperative CSF leakage, 148 (74.0%) ETSs were performed for skull base pathologies other than pituitary neuroendocrine tumor. The mean follow-up period was 34.4 months. Esposito grade 3 leakage was confirmed in 148 (74.0%) cases. NMFCT was used either with (67 [33.5%]) or without (133 [66.5%]) lumbar drainage. There were 10 cases (5.0%) of postoperative CSF leakage that necessitated reoperation. In 4 other cases (2.0%), CSF leakage was suspected but lumbar drainage alone successfully restored the condition. Multivariate logistic regression analyses revealed that posterior skull base location (P < 0.01, odds ratio 11.5, 95% CI 1.99–2.17 × 102) and craniopharyngioma pathology (P = 0.03, odds ratio 9.4, 95% CI 1.25–1.92 × 102) were significantly associated with postoperative CSF leakage. No delayed leakage occurred during the observation period except for 2 patients who underwent multiple radiotherapies. NMFCT is a reasonable alternative with long-term durability, though vascularized flap may be a better choice for cases in which vascularity of the surrounding tissues is significantly impaired due to interventions including multiple radiotherapies. [ABSTRACT FROM AUTHOR]