Objective The objectives of this study are: (1) to evaluate the prelacrimal recess-pterygoid window approach (PLR-PWA) for treating cerebrospinal fluid leaks and meningoencephaloceles (CSFLME) in the sphenoidal lateral recess (SLR). (2) To investigate the pneumatization of the SLR and its relationship with surrounding structures, including the lateral pterygoid plate and course of the maxillary nerve (V2).Methods This study retrospectively reviewed 13 patients (mean age [46.53 +/- 8.44] years) with spontaneous CSFLME in the SLR who underwent the PLR-PWA. The primary and secondary outcomes were surgical success rate and complications, respectively. The pneumatization of the SLR was classified according to Rhoton's classification, and its anatomical relationships with surrounding structures were analyzed using CT scans.Results The PLR-PWA was utilized in all patients, achieving a 100% surgical success rate at a median follow-up of 26.8 months. There were 6 (6/13, 54.55%) patients who had immediate postoperative hypoesthesia of the upper lip and face. In all cases, the pneumatization of the SLR extended beyond the lateral aspect of the lateral pterygoid plate, with the full lateral type SLR observed. Notably, in 3 out of 13 cases (23.08%), the V2 coursed below and across the SLR.Conclusion The PLR-PWA is indicated for patients with a full lateral type or well-pneumatized SLR and offers a direct and minimally invasive surgical route to the SLR. The degree of pneumatization of the SLR, the course of the V2, and its anatomical relationship to the SLR are essential factors to be considered when this approach is adopted.