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Rationale Chronic obstructive pulmonary disease (COPD) is the most common indication for domiciliary non-invasive ventilation (NIV), but long-term outcomes data are limited.Objective This multistate model analysis estimated the impact of NIV therapy continuation versus cessation on transitions between three different disease states.Methods Model data came from the French national health insurance reimbursement system database for individuals aged ≥40 years with COPD and ≥1 NIV reimbursement in 2015–2019.Measurement and main results Data from 49 503 patients started on NIV were included (median age 70 years, 51.2% male, median 1 exacerbation in the previous year). There were 80 361 severe exacerbations and 18 125 deaths (including 7805 in severe exacerbation). In multistate models, NIV continuation was associated with a significant reduction in transition to death, from severe exacerbation (HR 0.84, 95% CI 0.79 to 0.91) and without exacerbation (HR 0.88, 95% CI 0.83 to 0.93). NIV continuation versus cessation had no significant effect on transition between without exacerbation to severe exacerbation (HR 0.98, 95% CI 0.95 to 1.00) but was significantly associated with slower transition from severe exacerbation to without exacerbation (HR 0.87, 95% CI 0.84 to 0.89).Conclusion This multistate model analysis found that the long-term use of domiciliary NIV was associated with a lower risk of transitions to death, but was not associated with a reduction in recovery time after severe exacerbation. These data highlight the potential mortality benefits of long-term domiciliary NIV in COPD and can be used as one piece of evidence to support evidence-based guideline recommendations.