Introduction: Noninvasive home mechanical ventilation (NIHMV) has an impact on the health-related quality of life of patients with chronic global respiratory failure (CGRF) of different causes. There are generic and specific questionnaires for various respiratory diseases, and recently, in 2003, a patient-specific questionnaire was developed for NIHMV, called the Severe Respiratory Insufficiency (SRI) questionnaire, which has been shown to be reproducible and reliable and has been validated in several languages. Objective: Validate the Chilean version of the SRI questionnaire (IRS-cl) in adults with CGRF who use NIHMV. Methods: Cross-sectional study with non-probabilistic convenience sampling of stable patients from five regions of Chile. The IRS-cl and SF-36 (gold standard) questionnaires were applied, and demographic and ventilatory data were collected. Reliability was analyzed using Cronbach’s alpha and intraclass correlation (test-retest). Construct validity was tested using exploratory factor analysis (principal component extraction and equimax orthogonal rotation) and hypothesis testing (Mann-Whitney test). Convergent criterion validity was tested using Spearman’s rho. Results: The sample comprised 248 patients, 132 of whom were women (53.2%), with a median age of 62±17.5 years. There was a predominance of older adults, and 40% had a low education level. The completion time of the questionnaire was 18.8 ± 9.1 minutes (viable), and 100% of the items were answered. The questionnaire was self-applied by 46.8% of the sample. The IRS-cl showed very good overall reliability (0.95) and by scales (>0.7). It also showed a good correlation with the SF-36, with equivalent scales, a rotated matrix with 8 factors and hypotheses that explain the underlying constructs. Conclusions: The IRS-cl has good psychometric properties. It is feasible, valid and reliable for application to evaluate CGRF of various causes. It was found to be sensitive to assess the characteristics of the local population.