Objective: The National Institutes of Health Toolbox Cognition Battery (NIHTB-CB) measures reading, vocabulary, episodic memory, working memory, executive functioning, and processing speed. While previous research has validated the factor structure in healthy adults, the factor structure has not been examined in adults with neurological impairments. Thus, this study evaluated the NIHTB-CB factor structure in individuals with acquired brain injury. Method: A sample of 392 individuals (ages 18–84) with acquired brain injury (n = 182 TBI, n = 210 stroke) completed the NIHTB-CB along with neuropsychological tests as part of a larger, multisite research project. Results: Confirmatory factor analyses supported a 5-factor solution that included reading, vocabulary, episodic memory, working memory, and processing speed/executive functioning. This structure generally held in TBI and stroke subsamples as well as in subsamples of those with severe TBI and stroke injuries. Conclusions: The factor structure of the NIHTB-CB is similar in adults with acquired brain injury to adults from the general population. We discuss the implications of these findings for clinical practice and clinical research.