BACKGROUND AND PURPOSE The growing interest in testing new therapeutic agents for acute brain injury has lead to increased use of stroke scales. The reliability and validity of these measures need to be examined more completely. We used structural equation modeling, a technique that merges the analytic procedures of factor analysis and multiple regression, to examine the reliability and construct validity of the Middle Cerebral Artery Neurological Scale and the Scandinavian Neurological Stroke Scale used together as the Unified Neurological Stroke Scale. We also analyzed the predictive validity, sensitivity, and specificity of the scales in predicting mortality and functional outcome. METHODS We prospectively studied 84 consecutive patients admitted to a neurology/neurosurgery intensive care unit with intracerebral hemorrhage (n = 30), subarachnoid hemorrhage (n = 15), ischemic stroke (n = 15), and traumatic brain injury (n = 24). Patients were evaluated within 24 hours of admission and at 48-hour intervals until intensive care unit discharge. A total of 386 assessments were obtained. The Functional Independence Measure was administered by telephone 3 months after hospital discharge. RESULTS High levels of reliability and construct validity were observed for the majority of the Unified Stroke Scale items. Facial palsy and eye movement items had the lowest reliability and validity. Both the Middle Cerebral Artery and Scandinavian Scales were significant predictors of outcome. Sensitivity and specificity varied by diagnosis. Predictive validity of functional outcome was best in groups with ischemic and hemorrhagic stroke rather than traumatic brain injury and subarachnoid hemorrhage. CONCLUSIONS The Unified Stroke Scale demonstrates reliability and construct and predictive validity, and its use is supported in ischemic and hemorrhagic stroke. Structural equation modeling is an appropriate technique for use with scales of this type.