Background: The DLQI (Dermatology Life Quality Index) is the most commonly used instrument for evaluating the quality of life in dermatology. Skindex was developed as a multidimensional instrument with successive versions published, the most recent being Skindex-16 and Skindex-17, both derived from Skindex-29 through different techniques. This study aimed to compare the three instruments—the DLQI, Skindex-16, and Skindex-17—according to their psychometric performance to refine the assessment of the quality of life among dermatological patients.Methods: A methodological study compared the psychometric performance of the DLQI, Skindex-16 (Sk-16), and Skindex-17 (Sk-17) instruments among adults with dermatoses that were classified according to characteristic physical symptoms and psychological or social domains. Analyses were performed to assess internal consistency, correlation, test-retest reproducibility, and responsiveness according to classical psychometry and to test discrimination and difficulty according to the item response theory.Results: The sample consisted of 229 patients predominantly women (71%) of adult age (average 45 years) and intermediate phototypes (III and IV = 73%). The analyses of internal consistency for the instruments resulted in Cronbach-α coefficients >0.80. There was adequate test-retest reproducibility and responsiveness for all dimensions of the instruments. The IRT (Iten Response Theory) analysis indicated adequate ordering and discrimination (a >1.0) for all items of the DLQI, Sk-16, and Sk-17; four items of Sk-16 did not adequately adhere to the TRI model (p <0.01 ). The items with the greatest discrimination were q3 (domestic activities) and q5 (leisure activities) in the DLQI; F2 (desire to be with people) and E6 (annoyance) in Sk-16; and S4 (irritated skin), P5 (relationship), and P6 (autonomy of tasks) in Sk-17. The Sk-16 and Sk-17 instruments presented more items that registered mild impacts on the quality of life (b <-0.5).Conclusions: The DLQI, Sk-16, and Sk-17 presented adequate psychometric performance for the assessment of health-related quality of life in a Brazilian sample. The multidimensional instruments (Sk-16 and Sk-17) were more sensitive to mild impacts on quality of life.