<p>Reconstruction of skull base (SB) defects following endoscopic endonasal approaches (EEA) is critical to minimize postoperative complications. Porous high-density polyethylene (Medpor^®) implants have been employed for this purpose; however, their long-term complication rates and osteointegration outcomes remain unclear. A systematic review was conducted according to PRISMA guidelines across three databases, including studies involving SB reconstruction with porous polyethylene implants that reported complications and osteointegration outcomes. Additionally, a retrospective analysis was performed on 94 patients undergoing SB reconstruction in transsphenoidal surgery with Medpor (2008–2024). Osteointegration was assessed via imaging and clinical outcomes with a minimum follow-up of 1 year, as well as intraoperative findings in reoperated cases. Eleven studies (691 patients) were included, with reported postoperative complications including CSF leaks (2.9%), infections (2.3%), and rare implant extrusion or osteointegration failures (0.4%). In the institutional cohort, 25 of 94 patients (26.6%) required reoperation, with 17 undergoing reoperation at least 6 months post-implantation. All these patients were reoperated for pathology recurrence, except for one who was reoperated for spontaneous Medpor extrusion. Among these, 94% (16/17) had no evidence of osteointegration. Chronic nasal symptoms were reported in 13.4% of non-reoperated patients, with no cases requiring implant removal. One of the 17 reoperated patient had an additional surgery due to spontaneous Medpor Extrusion. The placement of the nasoseptal flap to cover Medpor did not appear to have a facilitating effect on its osseointegration; however, its role will need to be further studied. Medpor implants demonstrate acceptable long-term safety for EEA skull base reconstruction, with low rates of major complications. However, osteointegration appears infrequent (&lt; 8%) even over extended follow-up.</p>