According to various authors, the rate of sphenoid sinus defects ranges from 15 to 26%. In the sphenoid sinus, the most common defect localization is the lateral recess ― 35.3%. Regardless of the etiology and pathogenesis of lateral sphenoid sinus recess cerebrospinal fluid (CSF) leak, the treatment approach is aimed at plastic closure of the defect. Surgery in this area is associated with a high rate of recurrences (25%) due to a complex anatomical landscape and inapplicability of a direct approach. Purpose. The study purpose was to analyze our own experience in treating patients with CSF leak and meningoencephalocele in the lateral sphenoid sinus recess and, based on the obtained results, develop an algorithm for the treatment of this pathology. Material and methods. We retrospectively reviewed a series of 89 patients with CSF leak and meningoencephalocele in the lateral sphenoid sinus recess who were treated at the Burdenko Neurosurgical Institute in the period between 2001 and 2017. The demographic characteristics of patients, clinical data, and aspects of surgical treatment were analyzed. Treatment outcomes were assessed based on analysis of recurrences and postoperative complications. The obtained data were compared to the literature data. Results. In the series of 89 patients with CSF leak and meningoencephalocele in the lateral sphenoid sinus recess, the mean age was 49 years. Surgery through the transsphenoid approach was performed in 89 (74%) patients. There were 25 (28%) recurrences in this group. Nine (7%) patients underwent repair of a complex skull base defect using the transethmoidal approach; there were 3 (33%) recurrences. The transpterygoid approach was used in 22 (17%) patients; there were 3 (14%) recurrences in this group. Conclusions. Endoscopic endonasal repair is an effective technique for treating complex skull base defects in the lateral sphenoid sinus recess. The choice of an approach to the defect depends on the degree of pneumatization of the sphenoid sinus, surgeon’s experience, and availability of the necessary equipment and tools. The endoscopic transpterygoid approach is advisable to use in cases of excessive pneumatisation of the sinus with developed lateral processes and recurrent nasal CSF leak. This enables visualization of the defect edges in this hard-to-reach area and adequate repair.