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RATIONALE Non-invasive ventilation decreases the need for invasive mechanical ventilation and mortality among patients with chronic obstructive pulmonary disease but has not been well studied in asthma. OBJECTIVE To assess the association between non-invasive ventilation and subsequent need for invasive mechanical ventilation and in-hospital mortality among patients admitted with asthma exacerbation to the intensive care unit. METHODS We performed a retrospective cohort study using administrative data collected during 2010-2017 from 682 hospitals in the United States. Outcomes included receipt of invasive mechanical ventilation and in-hospital mortality. Generalized estimating equations, propensity-matched models, and marginal structural models were used to assess the association between non-invasive ventilation and outcomes. MEASUREMENTS AND MAIN RESULTS The study population included 53,654 participants with asthma exacerbation. During the study period 13,540 patients received non-invasive ventilation (25.2%; 95% CI 24.9%, 25.6%), 14,498 underwent invasive mechanical ventilation (27.0%; 95% CI 26.7%, 27.4%), and 1,291 died (2.4%; 95% CI 2.3%, 2.5%). Among those receiving non-invasive ventilation, 3,013 patients (22.3%; 95% CI 21.6%, 23.0%) required invasive mechanical ventilation after first receiving non-invasive ventilation, 136 of whom died (4.5%; 95% CI 3.8%, 5.3%). Across all models, the use of non-invasive ventilation was associated with a lower odds of receiving invasive mechanical ventilation (adjusted generalized estimating equation OR 0.36; 95% CI 0.32, 0.40) and in-hospital mortality (OR 0.48; 95% CI 0.40, 0.58). Those who received non-invasive ventilation prior to invasive mechanical ventilation were more likely to have comorbid pneumonia and severe sepsis. CONCLUSIONS Non-invasive ventilation use during asthma exacerbation was associated with improved outcomes but should be used cautiously with acute comorbid conditions.