The objective of the study was to examine the mediating effect of child dental use on the effectiveness of North Carolina Early Head Start (EHS) in improving oral health-related quality of life (OHRQoL). In total, 479 parents of children enrolled in EHS and 699 parents of Medicaid-matched children were interviewed at baseline when children were approximately 10 mo old and 24 mo later. In this quasi-experimental study, mediation analysis was performed using the counterfactual framework analysis, which employed 2 logit models with random effects: 1) for the mediator as a function of the treatment and covariates and 2) for the outcome as a function of the treatment, mediator, and covariates. The covariates were baseline dental OHRQoL, dental need, survey language, and a propensity score. We used in-person computer-assisted, structured interviews to collect information on demographic characteristics and dental use and to administer the Early Childhood Oral Health Impact Scale, a measure of OHRQoL. Dental use had a mediation effect in the undesired direction with a 2–percentage point increase in the probability of any negative impact to OHRQoL (95% confidence interval [CI], 0.3%-3.9%). Even with higher dental use by EHS participants, the probability of any negative impact to OHRQoL was approximately 8 percentage points lower if an individual were moved from the non-EHS group to the EHS group (95% CI, -13.9% to -1.2%). EHS increases child dental use, which worsens family OHRQoL. However, EHS is associated with improved OHRQoL overall. (author abstract)