Introduction Post-operative CSF leak still represents the main drawback of Endoscopic Endonasal Approach (EEA), and different reconstructive strategies have been proposed in order to decrease its rate. Objective To critically analyze the effectiveness of different adopted reconstruction strategies in patients that underwent EEA. Materials and methods Adult patients with skull base tumor surgically treated with EEA were retrospectively analyzed. Data recorded for each case concerned patient demographics, type of surgical approach, histotype, anatomical site of surgical approach, intra-operative CSF leak grade (no leak (INL), low flow (ILFL), high flow (IHFL)), reconstructive adopted strategy, Lumbar Drain positioning, post-operative CSF leak rate and intra/post-operative complications. Results A total number of 521 patients (January 2012-December 2019) was included. Intra-operative CSF leak grade showed to be associated with post-operative CSF leak rate. In particular, the risk to observe a post-operative CSF leak was higher when IHFL was encountered (25,5%; Exp(B) 16.25). In particular, vascularized multilayered reconstruction and fat use showed to be effective in lowering post-operative CSF leaks in IHFL (p 0.02). No differences were found considering INL and ILFL groups. Yearly post-operative CSF leak rate analysis showed a significative decreasing trend. Conclusion Intra-operative CSF leak grade strongly affected post-operative CSF leak rate. Multilayer reconstruction with fat and naso-septal flap could reduce the rate of CSF leak in high risk patients. Reconstructive strategies should be tailored according also to the type and the anatomical site of the approach.