Abstract Introduction and objectives The aim of this study was to assess the impact of psoriasis on health-related quality of life (HRQOL) using different questionnaires. Patients and methods Prospective observational study of patients with plaque psoriasis of at least 6 months’ duration stratified by active and stable disease. The patients were evaluated at baseline, 7 days, and 12 weeks. At the 3 visits, the investigators recorded sociodemographic and clinical data and the patients completed the following HRQOL questionnaires: the Dermatology Life Quality Index (DLQI), the Psoriasis Disability Index (PDI), and psoriasis quality of life questionnaire (PSO-LIFE). Results In total, 304 patients (182 with active psoriasis and 122 with stable psoriasis) were evaluated. The mean (SD) age was 45.3 (14.5) years, and 56.3% of the group were men. At baseline, the mean (SD) psoriasis and area severity index (PASI) score was 17.0 (7.4) in patients with active disease and 5.6 (5.3) in those with stable disease; a reduction was seen in PASI scores during the evaluation period ( P < .01). The mean (SD) score on the PSO-LIFE questionnaire increased significantly from 57.4 (20.4) to 72.2 (19.6) in patients with active psoriasis and from 76.4 (20.6) to 82.3 (18.3) in those with stable disease ( P < 0 .01 in both groups). The difference in standardized mean scores between the 2 groups was 0.79 for the DLQI, 0.62 for the PDI, and 0.85 for the PSO-LIFE questionnaire. The impact of psoriasis on HRQOL as assessed by the PSO-LIFE questionnaire was greater in patients with lesions in visible areas than in those with less visible lesions ( P < .01). Changes in PSO-LIFE and PASI scores were moderately and significantly correlated ( r = –0.4). Conclusions The impact of psoriasis on HRQOL is higher in patients with active disease. The PSO-LIFE questionnaire showed a greater tendency to discriminate between active and stable psoriasis than either the DLQI or the PDI. PSO-LIFE scores correlated significantly with lesion site and disease severity as measured by PASI.