Atopic dermatitis (AD) is a chronic relapsing condition that can have considerable effects on the patients’ quality of life (QOL). The aim of this study was to measure the health-related QOL in patients with AD, using generic and specific instruments, to compare the scores obtained by different instruments and to verify the relationship between them. We conducted a cross-sectional study of 132 outpatients with AD. To assess the QOL, Short Form 36 (SF-36), Dermatology Life Quality Index (DLQI) and Children’s Dermatology Life Quality Index (CDLQI) were administered. In order to assess the disease severity of AD, we used the Eczema Area and Severity Index (EASI) and physician assessment of disease severity. Stressful life events during the last 12 months were assessed with Paykel’s Interview for Recent Life Events. Patients with AD had inferior social functioning and mental health scores compared with the general population. The correlations between the DLQI and SF-36 were found for the mental components of the QOL. Increasing disease severity was associated with greater impairment in QOL in both, children and adults. Our study found the influence of the stressful life events on the role emotional of AD patients. These results demonstrate that AD influences health-related QOL, especially in children. This study supports the decision to use both generic and skin-specific instruments to assess the impact of AD on QOL.