This trial was conducted to carry out an age and etiology-based analysis of the clinical efficacy of non-invasive ventilation (NIV) in acute hypercapnic respiratory failure (AHRF). This single center, prospective, cohort study included patients aged >= 65 years with chronic obstructive pulmonary disease (COPD), acute cardiogenic pulmonary edema (ACPE), community-acquired pneumonia (CAP), bronchiectasis, and kyphoscoliosis, who were treated with NIV for AHRF in the intensive care unit within a 4-year period. From 496 patients aged 65 years or older treated with NIV for AHRF, 162 patients were included. Of the patients 71 were aged 65-74 years, 70 were 75-84 years, and 21 were aged >= 85 years. Of the patients 90 had COPD, 31 had ACPE, 19 had CAP, 15 had bronchiectasis exacerbation and 7 had kyphoscoliosis as the AHRF etiology. The treatment with NIV was successful in 119 patients. No significant difference was found between the age groups regarding NIV success rates (p = 0.803). An etiology-based analysis revealed that NIV was significantly more successful in the COPD and ACPE groups (p = 0.029, p = 0.035). A multivariate analysis revealed that Glasgow coma scale (GCS) (hazard ratio HR 0.215, 95% confidence interval CI: 0.104 to 0.442; p < 0.001), COPD assessment test (CAT) (HR 1.563, 95%CI: 1.229 to 1.987; p < 0.001), and acute physiology and chronic health evaluation (APACHE) I (TM) I (TM) (HR 1.009, 95%CI: 1.001 to 1.018; p = 0.031) as significant independent predictors of NIV failure in patients with COPD and AHRF. The efficacy of NIV was independent of age in patients aged >= 65 years with AHRF and NIV was most successful when the etiology of AHRF was COPD or ACPE. Dyspnea level, GCS, and APACHE-I (TM) I (TM) scores were independent predictors of NIV failure in COPD.