A better understanding of the clinical features associated with prolonged hospitalization in acute respiratory failure may allow for better informed care planning.To assess the incidence, mortality, cost and clinical determinants of prolonged hospitalization among patients with acute respiratory failure (ARF).Using the National Inpatient Sample (NIS) data from 2004 to 2014, we identified adults 18 years and older with International Classification of Disease, 9th Edition (ICD-9), codes for ARF requiring mechanical ventilation for at least two days (ICD-9 518.81 or 518.82, 96.7 or 96.04, and 96.05). Outcomes studied included incidence, in-hospital mortality, cost of hospitalization, and associated patient-level and hospital-level characteristics. Trends were assessed by logistic regression, linear regression and general linear modeling with Poisson distribution.Of the 5,539,567 patients with ARF, 77,665 (1.4%) had a prolonged length of stay, defined as ≥60 days (pLOS). Among pLOS, 52,776 (68%) survived to discharge. Over the study period, incidence of pLOS decreased by 48%, in-patient mortality decreased by 18%, per patient cost-of-care rose, but percent of the total cost of ARF care consumed by patients with pLOS did not significantly decrease (p=0.06). PLOS was more likely to occur in urban teaching hospitals (OR 6.8, CI 4.6-10.2, p<0.001), hospitals located in the Northeastern US (OR 3.6, CI 3.0-4.3, p<0.001), and among patients with Medicaid insurance coverage (OR 2.1, CI 1.9-2.4, p<0.001).From 2004-2014, incidence and mortality decreased among patients with ARF and pLOS, and while per patient costs rose, percent of total cost of care remained stable. There is substantial variation in length-of-stay for patients with ARF by US region, hospital teaching status and patient insurance coverage.