The effect of the Video-Feedback Intervention to Promote Positive Parenting and Sensitive Discipline (VIPP-SD) on daily cortisol production was tested in a randomized controlled trial with 130 families with 1- to 3-year-old children screened for their relatively high levels of externalizing behavior. Six 1.5-hr intervention sessions focusing on maternal sensitivity and discipline were conducted with individual families at their homes. Children in the intervention group showed lower cortisol levels, with a moderating role of the dopamine receptor D4 (DRD4) VNTR exon III polymorphism. The VIPP-SD program proved to be effective in decreasing daily cortisol production in children with the DRD4 7-repeat allele, but not in children without the DRD4 7-repeat allele. Our findings indicate that children are differentially susceptible to intervention effects dependent on the presence of the 7-repeat DRD4 allele.