Importance: "Not relevant" responses (NRRs) on the Dermatology Life Quality Index (DLQI) are common among patients with psoriasis and may be associated with an underestimation of disease severity. Objective: To evaluate the associations between (1) patient sociodemographic characteristics and the frequency of NRRs on the DLQI and (2) NRR frequency and treatment satisfaction. Design, Setting, and Participants: This cross-sectional study using data from the Dermatology Clinical Effectiveness Research Network from February 2010 to June 2011 assessed the responses on the DLQI of 1733 patients with psoriasis. Main Outcomes and Measures: Differences in the frequency of NRRs by sex, race/ethnicity, insurance type, income, educational attainment, marital status, and employment status were evaluated using the 2-tailed χ2 test. Multivariable logistic regression analysis was used to evaluate the associations between sociodemographic characteristics and having at least 1 NRR. Multivariable linear regression analysis was used to evaluate the association between having a DLQI score reclassified from 10 or less to more than 10 using the DLQI-Relevant scoring modification and the scores on the Treatment Satisfaction Questionnaire for Medication. Data were analyzed between July 2019 and November 2019. Results: Of 1733 patients with psoriasis, 879 (50.7%) were female, and 1470 (84.8%) were non-Hispanic white individuals. The DLQI items 6 (sport, 223 patients [12.9%]), 9 (sexual difficulties, 214 patients [12.3%]), and 7 (work or study, 126 patients [7.3%]) had the greatest frequency of NRRs. In multivariable logistic regression analysis, male sex (odds ratio [OR], 0.63; 95% CI, 0.48-0.82) and income of more than $100 000 (OR, 0.45; 95% CI, 0.26-0.79) were associated with decreased odds of NRRs. By contrast, single (OR, 1.85; 95% CI, 1.31-2.61) or widowed or divorced (OR, 2.60; 95% CI, 1.80-3.74) marital status and unemployed or disabled employment status (OR, 1.98; 95% CI, 1.35-2.89) were associated with increased odds of NRRs. Having a DLQI score that would be reclassified from 10 or less to more than 10 using the DLQI-Relevant scoring modification was associated with lower global satisfaction scores on the Treatment Satisfaction Questionnaire for Medication (coefficient, -9.8; 95% CI, -16.3 to -3.4). Conclusions and Relevance: There were sociodemographic differences in the frequency of NRRs on the DLQI among this cohort of patients with psoriasis. These differences may be associated with an underestimation of disease burden and treatment disparities owing to subsequent undertreatment among certain sociodemographic groups. Further study is needed to optimize the quality-of-life assessment among patients with psoriasis or other inflammatory skin diseases in diverse settings.