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Study Design: Biomechanical cadaveric study., Objective: The goal of this study was to analyze the effects of an endoscopic transpedicular approach with different drill diameters (6 and 8 mm) and compare them with the intact native side. In addition, the influence of bone quality on the resistance of the pedicle was investigated., Summary of Background Data: Clinical studies have repeatedly highlighted the benefits of endoscopic transpedicular decompression for downmigrated lumbar disc herniations. However, the biomechanical effects on pedicle stability have not been studied up to now., Materials and Methods: Twenty-four vertebras originating from four fresh-frozen cadavers were tested under uniaxial compression load in a ramp-to-failure test: (1) the tunneled pedicle on one side, and (2) the native pedicle on the other side. Twelve lumbar vertebrae were assigned to drill diameter of 6 mm and the other 12 to diameter of 8 mm., Results: The median ratio of sustained force for the operated side compared with the intact contralateral side is equal to 74% (63-88) for both drill diameters combined. An 8 mm transpedicular approach recorded an axial resistance of 77% (60-88) compared with the intact contralateral side ( P =0.002). A 6 mm approach resulted in an axial resistance of 72% (66-84) compared with the intact opposite side ( P =0.01). No significant difference between the two different drill diameters was recorded ( P =1). For all three subgroups (intact, 8 mm, 6 mm) the Hounsfield units-values and the absolute resistance force showed significant correlations (intact: ρ=0.859; P <0.001; 8 mm: ρ=0.902; P <0.001; 6 mm: ρ=0.835; P <0.001)., Conclusion: The transpedicular approach significantly reduces the axial resistance force of the pedicle, which may lead to pedicle fracture. Bone quality correlated positively with the absolute resistance force of the pedicle, whereas the influence of the drill hole diameter plays only a limited role., Competing Interests: M.F. reports being a Consultant for Incremed (Balgrist University Startup), Zimmer Biomet, Medacta, and 25 Segments (Balgrist Startup). The remaining authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)