Epidermolysis bullosa (EB) is a rare, inherited group of disorders characterized by blistering of the skin following friction or mechanical trauma. EB has a clinical and socio-economic impact on patients and their families. OBJECTIVES: To assess the Quality of Life (QoL) in patients with EB and to determine disease burden. METHODS: The study was an observational, cross-sectional postal survey. 185 patients were invited to participate. Different sets of questionnaires (SF-36, Skindex-29, GHQ-12, EQ-5D) were sent to patients according to age. The perceived severity of the disease was evaluated by patients or by the mothers of the younger EB children, using the Patient Global Assessment 5-point scale. Caregivers received the Family Strain Questionnaire (FSQ). RESULTS: A total of 125 respondents were analysed. EB patients showed lower values in physical components of SF-36, while the mental ones were not significantly impaired. Among EB types, junctional EB and severe generalized recessive dystrophic EB patients reported lower values and their General Health scale was significantly different from EB simplex. There were no significant differences among EB types/subtypes for Skindex-29 values. Females had a worse QoL compared to males in each Skindex-29 and SF-36 scales (p<0.05). GHQpositive cases were 48% among females, 16% among males (p=0.003); GHQpositive cases had a worse QoL compared to GHQnegative. The patient QoL and the family burden increased with increasing patient's perceived disease severity and with increasing patient's body surface involved. No differences were seen among EB types for the family burden. CONCLUSIONS: In EB patients mental components of SF-36 scores are similar to the normal population. The perceived disease severity and skin area involved are relevant for QoL independently by EB type/subtype. EB imposes a heavy burden on the caregiver and the family. Psychological support and close monitoring of QoL may help EB patients and their caregivers.