Background: Temperament has been associated with child anxiety in a number of studies; however, research examining possible mechanisms of effect using longitudinal designs is scarce. Objective: This study tested a theoretically-derived model of anxiety development spanning infancy (6 months) to early childhood (approximately 72 months) that includes temperamental reactivity (i.e., behavioral inhibition), temperamental self-regulation (i.e., effortful control), and gender. Methods: Data used in this study were collected in phase I and phase II from 1226 children and their caregivers by the National Institute of Child Health and Human Development for their prospective, longitudinal Study of Early Child Care and Youth Development. Structural equation modeling procedures were used to test whether effortful control mediated the relation between behavioral inhibition and anxiety and whether such mediation varied by gender. Results: Results provided support for the model, suggesting that one mechanism linking the modest association between behavioral inhibition in infancy to anxiety symptoms in early childhood is through diminished effortful control. Further, moderated mediation analyses indicated that this mechanism was apparent only for girls. Conclusions: Modulation of temperamental reactivity via effortful control may be a protective factor in the translation of early behavioral inhibition to childhood anxiety for girls.