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Background Accurate tools for patient stratification by likely outcome are needed to support complex decision-making and improve acute non-invasive ventilation (NIV) delivery. We assessed the potential of an emerging NIVO score tool to predict in-hospital mortality, to aid its validation in a real-world UK hospital population of ward-based NIV for acute exacerbations of COPD (AECOPD).Methods This was a retrospective observational cohort analysis on all consecutive admissions of patients with AECOPD, managed with NIV for acute hypercapnic respiratory failure (AHRF) at an acute teaching hospital. Clinical parameters were collected within our ongoing quality improvement project. Patients were split according to survival or in-hospital mortality. NIV failure and hospital mortality were modelled using logistic regression. NIV failure was defined as NIV withdrawal or intubation requirement due to clinical worsening clinical with NIV therapy.Results There were 249 unique patients and 314 AECOPD admissions with ward-based NIV. Across all admissions, NIV failure rate was 32.6%, in-hospital mortality 23.3%, and 1-year mortality 46.6. NIVO score was significantly associated with both NIV failure and in-hospital mortality, odds ratio (95% Confidence intervals) of 1.32 (1.14–1.53, p<0.001) and 1.54 (1.29–1.85, p<0.001), respectively. Older age was also associated with in-hospital mortality 1.07 (1.03–1.11, p<0.001) and current smoking associated with reduced risk, 0.41, (0.20–0.79, p=0.008).Conclusions We demonstrate the prospect of a novel NIVO tool to predict in-hospital mortality in a real-world population of ward-based NIV COPD patients. We show its potential utility to aid decision making and NIV delivery in new clinical pathways to meet the burden of COPD exacerbations.