Background and Purpose —Transcranial color-coded duplex sonography (TCCS) allows bedside imaging of intracranial hemodynamics and parenchymal structures. It provides reliable information regarding midline shift (MLS) in space-occupying hemispheric stroke. We studied the value of MLS measurement to predict fatal outcome at different time points after stroke onset. Methods —Forty-two patients with acute, severe hemispheric stroke were enrolled. Cranial computed tomography (CCT) and extracranial duplex sonography were performed on admission. TCCS was carried out 8±3, 16±3, 24±3, 32±3, and 40±3 hours after stroke onset. Lesion size was determined from follow-up CCT. Results —Twelve patients died as the result of cerebral herniation (group 1); 28 survived (group 2). Two patients received decompressive hemicraniectomy and were therefore excluded from further evaluation. MLS was significantly higher in group 1 as early as 16 hours after onset of stroke. Specificity and positive predictive values for death caused by cerebral herniation of MLS ≥2.5, 3.5, 4.0, and 5.0 mm after 16, 24, 32, and 40 hours were 1.0. Conclusions —TCCS helps to estimate outcome as early as 16 hours after stroke onset and thus facilitates identification of patients who are unlikely to survive without decompressive craniectomy. Because of its noninvasive character and bedside suitability, sonographic monitoring of MLS might be a useful tool in management of critically ill patients who cannot undergo repeated CCT scans.