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Intolerance of uncertainty (IU), a dispositional negative orientation toward uncertainty and its consequences, has been studied in adults, but research has only recently examined IU in youth. Despite some advances, little is known about the factor structure of measures of IU in youth. The present study used confirmatory factor analysis to examine the structure of IU as measured by the Intolerance of Uncertainty Scale for Children (IUSC; Comer et al., 2009) in a sample of youth (N = 368) 9–18 years of age (Mage = 12.47) with and without anxiety disorders and their mothers. Findings demonstrated multiple acceptable factor structures: a correlated factors 2-factor structure and a bifactor model where a general factor underlies all items. While the bifactor model provides better fit and reliability to the data, multivariate analyses indicated that the 2-factor structure distinguishes apprehensive anxiety regarding future events (prospective IU) from present-focused inhibition of behavior due to uncertainty and negative reactions to the presence of uncertainty (inhibitory IU); a total IU score predicted all anxiety domains for self- and parent-reports except for parent-report harm avoidance. Findings are discussed in terms of consistency of IU across adult and youth samples, and how results can inform treatment efforts and etiologic models of IU and anxiety.