Abstract: OBJECTIVE To investigate the pathogenic characteristics and risk factors of intracranial infection after craniotomy. METHODS A total of 479 patients undergoing craniotomy from May 2010 to May 2017 were selected. The clinical data of the patients were retrospectively analyzed. Lumbar puncture was performed to collect cerebrospinal fluid for pathogenic bacteria identification, and risk factors of infections were analyzed. RESULTS In 479 cases of craniotomy, 59 cases were intracranial infections, and the infection rate was 12.32%. Totally 70 strains of pathogens were isolated and cultured, among which 45 strains were gram-negative bacteria, accounting for 64.28%, 23 strains were gram-positive bacteria, accounting for 32.86%, and 2 strains were fungi, accounting for 2.86%. Acinetobacter baumannii had high resistant rates to amikacin and aztreonam, which were 95.65% and 86.96% respectively, and the resistant rates of Pseudomonas aeruginosa to ceftazidime and amikacin were 90.91% and 72.73%, respectively. Staphylococcus aureus had high resistant rates to penicillin and erythromycin, which were respectively 100% and 83.33%, and coagulase-negative Staphylococcus had high resistant rates to penicillin, erythromycin and levofloxacin, which were 100%, 85.71% and 85.71%, respectively. Univariate and multivariate analysis showed that operation time, cerebrospinal fluid leakage, antibiotic prophylaxis and drainage tube were independent risk factors of postoperative intracranial infections (P＜0.05). CONCLUSION The pathogens of intracranial infections after operation are mainly gram-negative bacteria, antimicrobial drugs should be rationally applied according to the characteristics of pathogens and drug resistance. According to independent risk factors, the corresponding countermeasures are adopted to reduce the incidence of postoperative intracranial infection.