Aim — the study aim was to analyze our own experience in treating patients with complex skull base defects accompanied by pneumocephalus and, based on the findings, to develop an optimal treatment approach for this pathology. Material and methods. We retrospectively reviewed a series of 30 patients with complex skull base defects accompanied by pneumocephalus who underwent inpatient treatment at the Burdenko Neurosurgical Institute in the period from 2001 to 2017. We analyzed demographic characteristics of patients (gender, age), clinical data (etiology, somatic and neuropsychiatric status, radiological data), and treatment aspects (conservative or surgical treatment, used approach, defect characteristics, reconstructive materials). Treatment outcomes were assessed based on analysis of changes in clinical manifestations, postoperative complications, and recurrences. The obtained data were compared to the results of literature review. Results. In the series of 30 patients with complex skull base defects accompanied by pneumocephalus, the mean age was 41 years (range, 17―68 years); there were 17 (59%) males and 13 (41%) females. Etiologically, there were 17 (59%) traumatic cases, 11 (36%) iatrogenic cases, and 2 (5%) spontaneous cases. Clinically, the patients presented with the following manifestations: psycho-neurological symptoms (41%), nasal cerebrospinal fluid (CSF) leak (36%), impaired consciousness (27%), and meningitis (23%). Eight patients with acute injuries underwent complex conservative treatment that included infusion, and anti-edema, vascular, metabolic, anticonvulsant, and antibacterial therapy. In cases of conservative treatment failure or tension pneumocephalus accompanied by abrupt worsening of the patient’s condition, surgical treatment was used. A total of 24 interventions (including revision surgery) were performed in 22 patients. All patients underwent endoscopic endonasal reconstruction of complex skull base defects. Tissues used for reconstruction included the fascia lata and adipose tissue (77%), fascia lata and cartilage/bone from the nasal septum (14%), and a pedicled nasoseptal flap (9%). The success rate of reconstructive interventions was 91%. There were 2 (9%) recurrences. Postoperative complications in the form of meningitis occurred in 4 (18%) patients. Conclusions. In the case of a nasal cerebrospinal leak history and worsening of the patient’s condition accompanied by common cerebral and psychiatric symptoms, the development of pneumocephalus should be considered first, the early diagnosis of which will facilitate choosing the correct treatment approach. In the case of acute injury in patients with the established diagnosis of pneumocephalus caused by gas-forming infection, conservative therapy is indicated in the early period after neurosurgical interventions with opening of the meninges. Tension pneumocephalus together with a skull base bone defect (according to CT) and a nasal CSF leak history is the indication for surgical treatment. In this case, the endoscopic endonasal technique is the method of choice.