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To describe the interference of herpes zoster (HZ) pain and discomfort with activities of daily living (ADLs) and health-related quality of life (HRQL) during the acute rash phase, and to quantify the relationship between acute HZ pain and discomfort and impaired ADLs and HRQL in older persons.Prospective, observational study of 160 HZ outpatients age ≥60 at 4 US study sites who completed the Zoster Brief Pain Inventory (ZBPI), Zoster Impact Questionnaire (ZIQ), McGill Pain Questionnaire, EuroQol, and SF-12 questionnaires on a predetermined schedule. Patients rated interference on a 0 to 10 scale for ADL items in the ZBPI and the ZIQ. Interference scores were averaged to create summary measures for the ZBPI items (ZBPI ADLI) and ZIQ items (ZIQ ADLI). A composite pain score was used in mixed-effects models analyses of the association between pain and discomfort and ADLI and HRQL measures during the first 35 days after HZ rash onset.HZ pain interfered with all ADLs but interference was greatest for enjoyment of life, sleep, general activity, leisure activities, getting out of the house, and shopping. For every 1.0 point increase in pain and discomfort intensity, there was a 0.69 and 0.53 point increase in ZBPI and ZIQ interference, respectively, and a 2.81 point, 1.57 point, and 1.95 point decrease in EuroQol, SF-12 physical, and SF-12 mental scales, respectively.Acute zoster pain and discomfort has a significant negative impact on functional status and HRQL in older adults. The magnitude of interference increases with increasing pain and discomfort intensity.