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Objectives were to examine whether 1) temperament and cortisol response in situations of unfamiliarity at 19 months predict social wariness and preference for solitude throughout childhood; 2) these predictive associations vary as a function of vagal regulation. Participants were 1199 children from the Quebec Newborn Twin Study, followed from 5 months to 10 years old (51% girl; 86% White). Findings show that behavioral inhibition to social unfamiliarity independently predicted both dimensions of social withdrawal in preschool. Low vagal suppression exacerbated the risk associated with negative affect manifested in unfamiliar situations to predict preference for solitude in preschool. In contrast, high vagal suppression increased the risk associated with strong cortisol response to unfamiliarity to predict social wariness in grade school.