Objective To evaluate the effect of various antimicrobial agents on preventing intracranial infection after craniocerebral surgery, and provide reference for antimicrobial prophylaxis in patients undergoing craniotomy. Methods Randomized controlled trials on prevention of intracranial infection after craniocerebral surgery were retrieved from domestic and foreign databases, after conducting literature screening, data extracting, and literature quality evaluation according to inclusion and exclusion criteria, Bayesian network Meta-analysis was performed with calling JAGS by GeMTC. Results A total of 3 214 patients after craniocerebral surgery in 11 studies were included in analysis, 159 patients had postoperative intracranial infection, including 33 patients in antimicrobial use group and 126 in control group, quality of literatures was good, consistency test showed that there was no obvious inconsistency between the direct and indirect comparison. Bayesian network Meta-analysis showed that antimicrobial prophylaxis could reduce the incidence of intracranial infection after craniocerebral surgery, but there was no significant difference between cephalosporin, clindamycin, fusidic acid, vancomycin, and penicillin. Conclusion Current evidence shows that preoperative intravenous injection of different antimicrobial agents had no significant difference in preventing intracranial infection after craniocerebral surgery, therefore, low-level antimicrobial agents can be selec-ted to prevent intracranial infection after craniocerebral surgery, more high-quality and large-sample studies are still needed to confirm this.