Objective This study aimed to assess the effectiveness of 3 endoscopic endonasal approaches for the management of cerebrospinal fluid (CSF) leaks and meningoencephaloceles in the lateral recess of the sphenoid sinus (LRSS). Study Design Retrospective study. Setting University hospital. Methods This study retrospectively reviewed 49 patients with CSF leaks and meningoencephaloceles in the LRSS. Three endoscopic surgical repair approaches were indicated based on 5 different Rhoton's types of the LRSS. The postoperative symptoms, complications, and follow-up outcomes were investigated and evaluated. Results The success rate of endoscopic surgical repair was 100% at a median follow-up of 75.06 (12-203.4) months. Endoscopic approaches to the LRSS included the prelacrimal recess (PLR) (18.37%), transsphenoidal (18.37%), and transpterygoid approaches (64.26%). All patients in the PLR approach (PLRA) group and most of the patients in the transpterygoid approach group had a full lateral type LRSS. Hypoesthesia and dry eyes were reported in 5 patients (55.56%) and 1 (11.12%) patient, respectively, from the PLRA group and in 6 (19.35%) and 5 (16.12%) patients, respectively, from the transpterygoid approach group. Conclusions Endoscopic closure is a safe and effective method for the treatment of CSF leaks and meningoencephaloceles in the LRSS. The transpterygoid approach and PLRA offer adequate exposure of the LRSS with extensive lateral pneumatization or a full LRSS. The endoscopic route of the PLRA is more direct than that of the transpterygoid approach. Careful preoperative imaging evaluation is crucial while selecting the optimal surgical approach for the repair of a skull base defect.