Abstract Introduction Brain midline shift (MLS) is a life-threatening condition that requires urgent diagnosis and treatment. We aimed to validate bedside assessment of MLS with Transcranial Sonography (TCS) in neurosurgical ICU patients by comparing it to CT. Methods In this prospective single centre study, patients who underwent a head CT were included and a concomitant TCS performed. TCS MLS was determined by measuring the difference between the distance from skull to the third ventricle on both sides, using a 2 to 4 MHz probe through the temporal window. CT MLS was measured as the difference between the ideal midline and the septum pellucidum. A significant MLS was defined on head CT as >0.5 cm. Results A total of 52 neurosurgical ICU patients were included. The MLS (mean ± SD) was 0.32 ± 0.36 cm using TCS and 0.47 ± 0.67 cm using CT. The Pearson’s correlation coefficient (r2) between TCS and CT scan was 0.65 (P <0.001). The bias was 0.09 cm and the limits of agreements were 1.10 and -0.92 cm. The area under the ROC curve for detecting a significant MLS with TCS was 0.86 (95% CI =0.74 to 0.94), and, using 0.35 cm as a cut-off, the sensitivity was 84.2%, the specificity 84.8% and the positive likelihood ratio was 5.56. Conclusions This study suggests that TCS could detect MLS with reasonable accuracy in neurosurgical ICU patients and that it could serve as a bedside tool to facilitate early diagnosis and treatment for patients with a significant intracranial mass effect.