Aim: To determine the risk factors for and the incidence, outcomes, and causative pathogens of post-craniotomy intracranial infection (PCII) in patients with brain tumors. Methods: A retrospective study was performed of 5723 patients with brain tumors who were surgically treated between January 2012 and December 2013 in Beijing Tiantan Hospital. The patients' demographics, pathohistological diagnoses, surgical procedures, postoperative variables, causative pathogens, and outcomes were evaluated. Results: The overall incidence of PCII was 6.8%, and 82.1% of all cases were diagnosed within two weeks after the craniotomy. Postoperative administration of antibiotics reduced the incidence of PCII. Independent risk factors included clean-contaminated craniotomy, prolonged operation (> 7 h), external cerebrospinal fluid (CSF) drainage/monitoring device placement, and postoperative CSF leakage. Patients <= 45 years old were more susceptible to infection. Compared with supratentorial tumors, tumors located in the infratentorial or intraventricular regions were more vulnerable to PCII. Gram-positive bacteria were the most common causative pathogens isolated from the CSF samples, accounting for 82.0% of the PCII cases. Conclusions: Risk factors for PCII can be identified early in the perioperative period. These findings raise the possibility of improving the clinical outcomes of patients with brain tumors who undergo craniotomy.