Objective: There are limited data on health-related quality of life (HRQL) in chronic obstructive pulmonary disease (COPD) patients with chronic hypercapnic respiratory failure during an admission requiring ventilatory support. The aim was to assess and compare the reliability and validity of the Clinical COPD Questionnaire (CCQ), Chronic Respiratory Questionnaire (CRQ), Maugeri Respiratory Failure-28 (MRF-28) Questionnaire, and Severe Respiratory Insufficiency (SRI) Questionnaire in patients with very severe COPD. Study Design and Setting: One hundred eighty hospitalized patients filled out the CCQ, CRQ, MRF-28, SRI, Groningen Activity Restriction Scale (GARS), Hospital Anxiety and Depression Scale (HADS), and the Medical Research Council Dyspnea Scale (MRC). Reliability was examined by assessing distribution of total scores, floor and ceiling effects, and internal consistency (using Cronbach alpha coefficient). Construct validity between questionnaires and also the other measurements were tested with Spe Results: All four questionnaires were feasible in this setting and had reasonable characteristics for distribution of total scores, floor and ceiling effects, internal consistency, and construct validity. On balance, the SRI scored best. Additionally, the SRI had a remarkable high explained variance by HADS, GARS, and MRC (73%). Conclusion: The SRI performed slightly better than the CCQ, CRQ, and MRF-28, which renders it the preferred questionnaire for scoring HRQL in patients with very severe COPD. (C) 2013 Elsevier Inc. All rights reserved.