Objective: Endoscopic spine surgery is an emerging technique of minimally invasive spine surgery. However, headache, seizure, and autonomic dysreflexia are possible irrigation-related complications following full-endoscopic lumbar discectomy (FELD). Pressure elevation through fluid irrigation may contribute to these adverse events. A validated experimental model to investigate parameters for guideline definition is lacking. This study aimed to create an experimental setting for FELD with pressure assessments to prove the concept of repeatable and sensitive measurement of intracranial, intra- and epidural pressures during spine endoscopy.Methods: To measure intradural pressure, catheters were introduced through a sacral approach and advanced to lumbar, thoracic, and cervical levels in human cadavers. Similarly, lumbar epidural and intracranial probes were placed. The dural sac was filled with Ringer solution to a physiologic pressure of 15 cmH2O. Lumbar endoscopy was performed on 3 human cadavers at the L3–4 level. Pressure changes were measured continuously at all sites and the effects of backflow-occlusion were monitored.Results: Reproducibility of the experimental model was validated with catheters at the correct locations and stable compartmental pressure baselines at all levels for 3 specimens (mean±standard deviation: 1.3±2.9 mmHg, 9.0±2.0 mmHg, 6.0±1.2 mmHg, respectively). Pressure increase could be detected sensitively by closing the system with backflow-occlusion.Conclusion: An experimental setup for feasible, repeatable, and precise pressure measurement during FELD in a human cadaveric setup has been developed. This allows investigation of the effects of endoscopic techniques and pump pressures on intra-, epidural and intracranial pressure and enables ranges of safe pump pressures per clinical situations.