OBJECTIVE： To observe clinical efficacy and safety of intrathecal injection of meropenem combined with vancomycin for intracranial infections after craniotomy. METHODS： In retrospective analysis， 46 patients with intracranial infections after craniotomy selected from our hospital during May 2014 to Jun. 2016 were divided into control group （20 cases） and observation group （26 cases） according to treatment method. Control group was given Vancomycin hydrochloride for injection 1.0 g， ivgtt， bid+Meropenem for injection 2.0 g， ivgtt， tid. After cerebrospinal fluid release of lumbar cistern drainage， observation group was given Vancomycin hydrochloride for injection 20 mg slowly， and the given Meropenem for injection 20 mg， bid， after washing tube with 0.9％ Sodium chloride injection 2 mL. Both groups received treatment for 2 weeks. Cerebrospinal fluid bacterial culture， clinical efficacy， healing time and treatment cost were observed in 2 groups， and the occurrence of ADR and sequela in 6 months after treatment were recorded. RESULTS： The positive rate of cerebrospinal fluid bacterial culture of 46 patients was 45.7％. The healing rate of observation group （92.3％） was significantly higher than that of control group （65.0％）. Healing time and treatment cost of observation group were significantly shorter or lower than control group； and total incidence of ADR （7.7％） was also significantly lower than control group （40.0％）， the incidence of sequelae （3.8％） was significantly lower than control group （20.0％）， with statistical significance （P＜0.05）. CONCLUSIONS： Therapeutic efficacy of intrathecal injection of meropenem combined with vancomycin is superior than intravenous administration for intracranial infections after craniotomy， can significantly shorten the treatment time and reduce treatment cost with good safety.