Objective: To investigate the clinical significance of intraoperative B-ultrasound real-time monitoring in craniotomy for patients with severe traumatic brain injury (sTBI). Methods: From March 2017 to June 2019, 64 patients with sTBI who met the admission criteria were included in the study. Craniotomy and/or decompressive craniectomy were performed. According to the application of real-time B-ultrasound-guided surgery, the patients were randomly divided into 2 groups:ultrasound group (n=32) and control group (n=32). The operation time, the number of new hematoma during and after operation, the probability of bone flap removal, the probability of second operation and Glasgow Coma Scale (GCS) score were recorded. Glasgow Outcome Scale (GOS) was used to evaluate the prognosis and calculate the good prognosis rate. Results: In the ultrasound group, 32 cases were successfully operated under the guidance of B-ultrasound, and the detection rate of new hematoma was 76% (19/25). The rate of hematoma clearance rate > 90%[84.38% (27/32) vs. 59.38% (19/32); χ2=4.947, P=0.026], GCS score at 3 d after operation (11.38 ±3.54 vs. 9.19 ±3.81; t=2.382, P=0.020) and good prognosis rate at discharge[56.25% (18/32) vs. 31.25% (10/32); χ2=0.077, P=0.038] in the ultrasound group were higher than those in the control group, but there were no significant differences in the operation time, the probability of bone flap removal and the probability of second operation between 2 groups (P > 0.05, for all). Conclusions: Intraoperative real-time B-ultrasound-guided surgery can improve the prognosis of patients with sTBI. Copyright © 2020 by the Editorial Board of Chinese Journal of Contemporary Neurology and Neurosurgery.