Patients with chronic wounds are significantly impaired in their health-related quality of life (HRQoL). The validated Wound-QoL questionnaire allows assessing the impact of chronic wounds on different aspects of HRQoL including physical, psychological, and everyday life-related impairments. The aim of our study was to investigate associations of these HRQoL dimensions with age, sex, and particularly wound genesis. In this retrospective, cross-sectional, multicentre study, Wound-QoL questionnaires from clinical routine of patients with venous leg ulcers, arterial leg ulcers, mixed leg ulcers, and diabetic foot ulcers (DFU) were evaluated. Effects of wound genesis, sex, and age were assessed with analysis of variance as well as correlation and multiple linear regression analyses. The completed questionnaires of 381 patients (f = 152/m = 229; mean age 68.9) were included. The wound genesis groups showed significantly different distributions of age and sex. We also found significant differences between those groups in everyday life-related QoL, with the greatest impairments in patients with DFU. Physical QoL scores showed significant differences between men and women depending on diagnosis group: in patients with venous leg ulcers, women had greater impairment of physical QoL than men. Independent of the underlying diagnosis, women had significantly higher scores in the psychological subscale as well as in the Wound-QoL sum scale. Within the subgroup of arterial leg ulcer patients, overall HRQoL sum score was significantly worse in older patients. Regression analyses supported negative effects of DFU diagnosis and female sex on HRQoL. Our data offer evidence that HRQoL shows clinically relevant differences between patients with chronic wounds of different genesis. Moreover, our data revealed that HRQoL is associated with age and sex, which should be considered when treating the patient groups. In order to be able to capture these important aspects and to offer individualised and patient-oriented treatments, the Wound-QoL should be implemented as a quick and uncomplicated standard instrument in daily routine. Patients with chronic wounds are significantly impaired in their health-related quality of life. Validated Wound-QoL questionnaire is a quick and easy-to-use instrument for daily practice. Wound-related quality of life shows clinically relevant differences between patients with chronic wounds of different genesis. Wound-related quality of life is associated with age and sex, which should be considered when treating these patient groups. Health-related quality of life should be regularly objectified in all patients with chronic wounds with a validated measuring instrument., (© 2021 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)