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Atopic dermatitis (AD) has an established impact on health-related quality of life (HRQoL) and family QoL.This study was designed to investigate gender differences in health-related and family QoL in children with AD.Cohorts of 25 girls and 25 boys with AD aged <4 years were selected from 102 children with AD. Children in the girls' and boys' groups were individually matched across groups for age and severity of AD according to their scores on the SCORAD Index (SCORing of Atopic Dermatitis). The children's parents filled in the Infants' Dermatitis Quality of Life (IDQoL) Index and the Dermatitis Family Impact (DFI) questionnaires.The impact of AD on QoL (P < 0.05) and family QoL (P < 0.05) was more severe in girls. The severity of AD as assessed by the parents was equal in both groups. More parents of girls reported that AD impacted on the “child's mood” (P < 0.05) and “enjoying family activity” (P < 0.05). “Child's mood” and “sleep disturbance” were highly scored by parents of girls (P = 0.01 and P < 0.05, respectively). Severity of AD as assessed by parents and IDQoL Index scores correlated with SCORAD scores in both groups. Scores on the DFI correlated with patient age in boys. The child's age correlated with the emotional distress of parents in both groups and had an impact on “relationships in the family” in girls only. Several DFI items and overall family QoL correlated with patient age in boys.The impact of AD on QoL and family QoL was more severe for girls. Relationships between parents progressively worsen with patient age in girls. Reported gender differences should be further investigated and may influence educational programs and advice given to parents of children with AD.