This study investigated moderators of change in an empirically supported family-centered intervention (the Family Check-Up) for problem behavior in early childhood. Participants were 731 2- to 3-year-olds (49% girls; 28% African American, 50% European American, 13% biracial) from low-income families and had been screened for risk of family stress and early-onset problem behavior. They were randomized to the Family Check-Up intervention or to a no-intervention control group. Latent growth models examined sociodemographic and parent psychological risk factors as potential moderators of change in problem behavior between ages 2, 3, and 4. Results revealed 2 moderators of intervention effectiveness. Caregivers with the lowest educational levels were more responsive to the family-centered intervention, and 2-parent families were more responsive to the intervention. Other risk factors showed no predictive effects. Overall, findings suggest that this brief family-centered intervention can be equally effective in reaching the most distressed and most disadvantaged families, compared to those who are more advantaged. However, results suggest that more attention may be needed to address the intervention needs of single parent families in reducing problem behavior in early childhood.