Objectives: To evaluate the molecular epidemiology and mortality risk factors of nosocomial meningitis (NM) induced by multi-drug resistance Enterobacteriaceae (MDRE) in China. Methods: We performed a multi-center study of MDRE NM patients in 2 neurosurgical centers in China from 2014 to 2019. Molecular and phenotype microbiology epidemiology of each MDRE were reviewed and tested, and 21 clinical variables on mortality risk factors were extracted and evaluated by multivariate Cox analysis for NM. Results: In total, 90 MDRE NM patients were included in this study. Klebsiella (K.) pneumoniae occupied the highest proportion (51.11%, 46/90), 44 (44.44%) were meropenem-resistant, ceftriaxone resistance in target MDRE was relatively high (92.22%, 83/90), blaKPC (67.50%, 27/40) was the predominant carbapenem resistance gene, and blaCTX-M-1, blaTEM and blaCTM-M-9 were the three most popular extended spectrum β-lactamases (ESBLs) producing genes of the MDRE. Multivariate Cox analysis showed that external ventricular drainage (EVD, odds ratio (OR) 2.524, 95% confidence interval (CI) 1.101-5.787, P = 0.029) and Glasgow Coma Scale (GCS) ≤8 (OR 4.033, 95% CI 1.526-10.645, P = 0.005) were mortality risk factors of MDRE NM. Conclusions: NM caused by MDRE is an important sign of the failure of neurosurgery, and MDRE has multiple drug resistance genotypes, and EVD and GCS≤8 are independent mortality risk factors of MDRE NM, which deserves the attention of microbiologist and neurosurgical clinicians.