Objective To investigate the occurrence of intracranial infection after craniocerebral operation and related risk factors, and to provide a basis for timely prevention and control of intracranial infection.Methods Univariate and multivariate logistic regression analyses were performed to investigate the association of age, type of operation, Glasgow Coma Scale (GCS) score, American Society of Anesthesiologists score, with or without postoperative cerebrospinal fluid drainage, time of operation, number of operations, and existence or absence of postoperative leakage of cerebrospinal fluid with intracranial infection in 257 patients undergoing craniocerebral operation.Results Intracranial infection occurred in 25 patients. Univariate logistic regression analysis showed that type of operation, GCS score, with or without postoperative cerebrospinal fluid drainage, number of operations, and existence or absence of postoperative leakage of cerebrospinal fluid were associated with the occurrence of postoperative intracranial infection (all P<0.05); multivariate logistic regression analysis showed that the risk factors for occurrence of postoperative intracranial infection were postoperative cerebrospinal fluid drainage (P=0.026), postoperative leakage of cerebrospinal fluid (P=0.007), GCS score ≤9 (P=0.013), time of operation >4 h (P=0.042), second operation (P=0.049), and emergency operation (P=0.029).Conclusions Intracranial infection is caused by the combined effect of various factors during craniocerebral operation. Timely prediction and evaluation, prevention, and control should be provided in clinical practice to reduce the incidence of postoperative intracranial infection.