OBJECTIVE： To compare the clinical efficacy， safety and economy of vancomycin and linezolid in the treatment of intracranial infections after neurosurgery operation. METHODS： Clinical data of 53 patients with intracranial infections receiving vancomycin （32 cases） and linezolid （21 cases） after neurosurgery from Jan. 2015 to Nov. 2017 were collected from medical record inquiry system of Xijing Hospital of Air Force Medical University. Pathogen detection， clinical efficacy and cerebrospinal fluid indexes were compared between 2 groups before and after treatment. The occurrence of ADR was observed in 2 groups， and treatment duration of total effective patients and total cost of antibiotics was compared. RESULTS： The bacterial culture of cerebrospinal fluid was positive in 20 patients， with positive rate of 38.46％（20/52）. There was no statistical significance in pathogen positive rates and total effective rates between 2 groups （P＞0.05）. White blood cell count， red blood cell count， neutrophil percentage and the contents of protein in cerebrospinal fluid of 2 groups were lower than before treatment， while the contents of glucose were higher than before treatment， with statistical significance （P＜0.05）， besides patients with therapy failure. But there was no statistical significance in these indexes between 2 groups after treatment （P＞0.05）. There was no statistical significance in duration of antibiotics use and incidence of ADR between 2 groups （P＞0.05）. The total cost of antibiotics in vancomycin group was significantly lower than linezolid group， with statistical significance （P＜0.05）. CONCLUSIONS： The effectiveness and safety of vancomycin are similar to linezolid in the treatment of Gram-positive bacterial intracranial infection after neurosurgery. Vancomycin is superior to linezolid in terms of economy. If patients do not have obvious liver or kidney insufficiency， or allergies， etc.，vancomycin should still be the first choice for treatment.