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Effortful control (EC), or the trait-like capacity to regulate dominant responses, has important implications for children’s development. Although genetic factors and parenting likely influence EC, few studies have examined whether they interact to predict its development. This study examined whether the DRD4 exon III variable number tandem repeat polymorphism moderated the relation between parenting and children’s EC. Three hundred and eighty-two 3-year-olds and primary caregivers completed behavioral tasks assessing children’s EC and parenting. Children’s DRD4 genotypes moderated the relation between parenting and EC: Children with at least one 7-repeat allele displayed lower EC in the context of negative parenting than children without this allele. These findings suggest opportunities for modifying early risk for low EC.