The aim: The purpose of this study was to assess the safety of propofol use during neurosurgical operations of different durations. Materials and methods: 72 patients were divided into three groups depending on the type of operations; it were group 1 (ventriculostomy), group 2 (hematoma removal), and group 3 (tumor removal), the anesthesia durations in these groups were 65±5 min, 145±7 min and 225±10 min, respectively. Total propofol doses in patients of groups 1, 2, and 3 were 452±22 mg, 710±42 mg, and 966±51 mg, respectively. Before intervention and 1 h post operation, blood gas composition, serum levels of transaminase, triglycerides, creatine phosphokinase, and potassium, rate of urine output, level of mean arterial pressure, and heart rhythm rate were determined. Results: No significant deviations concerning hemodynamic indicators, blood gas composition, changes of creatine kinase activity were found for any group patients during the perioperative period. The rate of urine output in all patients reached above 0.5 ml/kg/h without saluretics use. The deviated transaminase values returned to their normal ones during 24 h post intervention. The triglycerides levels were in normal range proving the absence of propofol doses used on the lipid metabolism. Conclusions: Anesthetic protection of neurosurgical interventions using propofol in doses 2.5-3 mg/kg and 3.60.3 mg/kg/h for induction anesthesia and for anesthesia support, respectively, is safe and does not lead to dangerous undesired consequences. However, the propofol use for prolonged patient sedation and his/her adaptation for prolonged lung ventilation needs further studies.