Abstract The Dermatology Life Quality Index (DLQI) was first published in 1994, and, since that time, it has become the most widely used patient-reported outcome measure worldwide in dermatological studies, owing to its robustness, simplicity and ease of use. This study is the first to review systematically evidence of DLQI validation. MEDLINE, Cochrane Library, Embase, Web of Science, SCOPUS, CINAHL (EBSCO) and PsycINFO were searched for relevant peer-reviewed publications in English, combined into EndNote and filtered for inclusion and exclusion criteria. The study followed PRISMA guidelines, and the study protocol was prospectively published in PROSPERO. A bespoke REDCap database was created, and data from included studies were independently extracted into this by two reviewers. COSMIN guidelines were used to determine bias in studies, and only those studies that reported COSMIN-accepted methods of validation were included. A total of 1262 articles were found from online searches; on screening, 69 met the eligibility criteria, describing 19 216 patients. Studies were conducted in at least 26 different countries, with 13 in the USA, 8 in China, and 5 each in the UK, Brazil and Hungary. Most patients were recruited in hospitals (30.4%), clinics (21.7%) and outpatient departments (10.1%), and 22.5% in other settings; 13.0% was not specified. Twenty-nine studies were multicentred. Most studies (n = 38) collected data specifically for validation, five used data from randomized controlled trials, seven were case–control studies and one was an open-label study. One study was validation of a translation, and five were of cross-cultural adaptation. Psoriasis was the most common disease studied (n = 19; 27%), along with 19 other diseases. The UK English version of the DLQI was used in 18 studies, and 20 other language versions were also used in the other studies. Factor analysis was done in 21 studies, Rasch/item response theory (n = 5), test–retest (n = 14), Cronbach’s alpha (n = 33), known group (n = 19), convergent (n = 10), concurrent (n = 3), divergent (n = 2), content (n = 7), criterion (n = 2) and face (n = 2) validation and responsiveness (n = 15). COSMIN risk of bias showed that few studies met the current rigorous requirements of the guidelines. Extensive evidence of validation of the DLQI is provided to inform researchers’ decisions concerning its use. Recommendations for improving the research methodology and reporting of DLQI validation are also given.