Objective To investigate the efficacy and safety of intravenous combined with intrathecal injection of antibiotics in the treatment of central nervous system infection (central nervous system infection ,CNSI) after spinal surgery. Methods The general data of postoperative CNSI patients who underwent spinal surgery in our department from January 2019 to January 2021 were collected to observe the clinical effects and complications of intravenous combined with intrathecal injection of antibiotics in lumbar puncture. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell count, neutrophil ratio and white blood cell count in cerebrospinal fluid were compared before treatment, after the first intrathecal injection and at the end of treatment. Results A total of 9 patients were included in this study, including 4 males and 5 females, aged from 7 to 73 years (mean 53.89±23.48 years). All patients were cured and discharged from hospital and there was no recurrence during follow-up. There were 2 cases of cerebrospinal fluid leakage, 2 cases of secondary oral fungal infection, 1 case of headache and 1 case of mental symptoms. Before treatment, after the first intrathecal injection and at the end of treatment, the CRP was 81.13±33.06 mg/L,50.59±24.85 mg/L,3.05±1.30 mg/L respectively, ESR was 36.00±7.90mm/h,24.56±7.50mm/h, 6.56±2.60mm/h respectively and the blood routine white blood cell count was (14.95±6.60)x109mg/L,(12.33±6.10)x109mg/L,(5.48±1.47)x109mg/L respectively. The ratio of neutrophils was 0.87±0.04,0.80±0.05,0.61±0.10 respectively and the number of leukocytes in cerebrospinal fluid was 3620±3608/mm3, 1546±1561/mm3, 15.78±13.78/mm3 respectively. There were significant differences among the three groups (P < 0.05).Conclusion Intravenous injection of antibiotics combined with lumbar puncture intrathecal injection in the treatment of CNSI after spinal surgery can obtain satisfactory clinical effect, less complications and higher safety .