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OBJECTIVE To explore the efficacy of multi-layer skull base reconstruction after endoscopic transnasal surgery for invasive pituitary adenomas (IPAs). CLINICAL RATIONALE FOR THE STUDY Skull base reconstruction for IPAs. MATERIAL AND METHODS This retrospective analysis involved 160 patients with IPAs who underwent operations from October 2018 to October 2020. All patients were diagnosed with IPAs by pituitary enhanced magnetic resonance imaging, and all tumours were confirmed to be Knosp grades 3a, 3b, or 4. The experimental group and the control group comprised 80 patients in each, and we used different methods to reconstruct the skull base in each group. The comparison indicators included cerebrospinal fluid leakage, sellar floor bone flap (or middle turbinate) shifting, delayed healing of the skull base reconstructed tissue, nasal discomfort, and epistaxis. We used the chi-square test, and p < 0.05 was considered statistically significant. RESULTS In the experimental group, cerebrospinal fluid leakage occurred intraoperatively in 73 patients, two of whom had cerebrospinal fluid leakage postoperatively. Brain CT 12 months postoperatively showed no sellar floor bone flap (or middle turbinate) shifting. Endoscopic transnasal checks performed seven days after surgery showed that the skull base reconstructed tissue had healed in 74 patients and had failed to heal in six. However, endoscopic transnasal checks showed that all six of these patients' pedicled nasoseptal flaps had healed well by 14 days after surgery. Other sequelae comprised nasal discomfort in four patients, and epistaxis in four. In the control group, cerebrospinal fluid leakage occurred intraoperatively in 71 patients, 14 of whom had cerebrospinal fluid leakage postoperatively. Brain CT 12 months postoperatively showed floor bone flap (or middle turbinate) shifting in 12 patients. Endoscopic transnasal checks performed seven days after surgery showed that the skull base reconstructed tissue had healed in 65 patients. In 12 patients, pedicled nasoseptal flaps had healed well by 14 days after surgery, while the remaining three patients required reoperation. Other sequelae comprised nasal discomfort in five patients, and epistaxis in six. CONCLUSIONS This new method of multi-layer skull base reconstruction could play an important role in endoscopic transnasal IPA surgery.