Background It has been confirmed that the concentration of cefepime in cerebrospinal fluid (CSF) could reach the 10% of its concentration in plasma, exceeding the inhibitory concentration to 90% of organisms (MIC90) for common bacteria.However, the blood-brain barrier (BBB) penetration ability of cefepime is still unclear. The aim of this study was to measure the CSF concentration of cefepime in patients after neurosurgical operations, and to determine the penetration of the drug through an incomplete BBB.Methods Eight patients who received ventricular drainage (VD group) and 5 who underwent lumbar puncture drainage (LPD group) were enrolled into this study. Cefepime (2 g) was injected intravenously in 30 minutes after the neurosurgeries. The concentrations of cefepime in the CSF and plasma were measured by high-pressure liquid chromatography (HPLC) at different time points.Results The CSF concentrations of cefepime at different time points in the VD group were significantly higher than those in the LPD group (P＜0.05). In the VD group, the concentration of cefepime in CSF reached the peak ((22.54±14.06)μg/ml) at 1 to 2 hours after the injection, while in the LPD group at 4 hours ((5.61±3.73) μg/ml). In both groups, the peak was higher than the MIC90 of most common bacteria in intensive care unit. The ratio of CSF to plasma cefepime concentrations ranged from 0.30 to 2.14 in the VD group and 0.03 to 1.14 in the LPD group.Conclusion After neurosurgeries, CSF concentration of cefepime can reach a therapeutic level. Thus, the drug could be used to prevent and treat postoperative intracranial infection.