This cross-sectional study was undertaken to determine the association between clinical and social variables and health-related quality of life (HRQoL) in patients suffering from leg ulceration. Patients were given a questionnaire to complete that incorporated clinical and social factors with the Nottingham Health Profile (NHP). The mean difference in NHP scores was calculated between categories for social and clinical variables, after adjustment for the patients' ages and gender. The 758 patients (mean age = 74.6 years, 64% women) had leg ulceration present for a median of 10.5 months (range, 0.5-708). Bodily pain (mean difference [d] = 8.9, P < .001), emotion (d = 4.7, P = .009) and social isolation (d = 0.032) were associated with large (>10 cm(2)) ulceration, whereas pain (P = .022) and social isolation (P = .008) were significantly associated with long ulcer duration. Patients treated by district nurses in community clinics experienced significantly less pain (d = -11.5, P < .001) and better sleep quality (d = -8.3, P = .006) than other patients did, whereas patients being treated by district nurses in the patients' own homes experienced deficits in pain (d = 11.4, P < .001), sleep quality (d = 8.8, P = .001), and mobility (d = 6.3, P = .002). There is some evidence to support the notion that large, long-duration ulceration leads to poorer HRQoL. Patients treated in nurse-led leg ulcer clinics experienced better HRQoL than did patients treated in other clinical areas. This observation needs to be evaluated more fully in future studies.