Background Various pathologies, including cerebrospinal fluid leaks and meningoencephaloceles, may arise in the lateral recess of the sphenoid sinus (LRSS), which may be accessed via an endonasal transpterygoid approach. The objective of this study was to evaluate the feasibility of accessing the LRSS via an endoscopic prelacrimal approach. Furthermore, we hypothesized that this approach may protect the pterygopalatine ganglion and vidian nerve. Methods Five cadaveric heads (9 sides) with a well-pneumatized LRSS were identified and an endonasal prelacrimal approach was performed. The infraorbital nerve, at the orbital floor, served as a critical landmark. After identification of the foramen rotundum at the pterygoid base, the vascular compartment of the pterygopalatine fossa and the pterygopalatine ganglion were displaced inferomedially and superomedially, respectively. Drilling of the bone inferomedial to the foramen rotundum allowed entry into the LRSS. Results The average distances from the prelacrimal window to the pterygoid base and the posterior wall of the LRSS were 6.22 +/- 0.39 cm and 7.16 +/- 0.50 cm, respectively. The average areas of the bony prelacrimal window and pterygoid base window were 4.33 +/- 0.32 cm(2) and 0.73 +/- 0.10 cm(2), respectively. The LRSS could be accessed using a 0-degree endoscope, and pterygopalatine neurovascular structures, including the pterygopalatine ganglion and vidian nerve, could be preserved on all 9 sides. Conclusion Our findings suggest that an endonasal prelacrimal approach provides a reasonable alternative to access the LRSS while preserving the vidian nerve and pterygopalatine ganglion.