OBJECTIVES: High velocity nasal insufflation (HVNI), a form of high flow nasal cannula, can provide respiratory support to many patients with respiratory failure more comfortably than non-invasive positive pressure ventilation (NIPPV). Our objective was to assess clinical resource utilization and cost impact to payers and providers associated with the use of HVNI versus NIPPV in the treatment of acute-care patients presenting to the emergency department with acute respiratory failure. METHODS: Treatment-specific resource utilization data were collected in a randomized multi-center trial of 204 patients conducted in the United States. Patient-level reimbursement data were calculated based on Medicare fee schedules. Hospital-specific resource costs were collected from participating sites and published literature. For both strategies, unit-specific length of stay, intubation rates and duration were analyzed. Cost differences were evaluated from the Medicare payer and hospital perspectives. Differences in non-normally distributed data were assessed with the Wilcoxon ranksum (Mann Whitney U) test. RESULTS: HVNI was found to be associated with the same total length of stay (6.75 vs. 6.01 days, p=0.51) and the same utilization of cost-intensive ICU care (1.50 vs. 1.85 days, p=0.56), a trend towards reduced intubation rates (5.7% vs. 13.0%, 0.095), and a potentially clinically important, but not statistically significant, reduction in ventilation hours for intubated patient (82.3 vs. 127.3 hrs., p=0.69). Resulting mean costs to payers ($10,633 vs. $11,848, p=0.41) and hospitals ($12,122 vs. $12,655) were similar. CONCLUSIONS: Our analysis suggests that HVNI, at outcomes clinically comparable to NIPPV, is associated with no additional cost or resource utilization. Potential decreased need for intubation and ventilation, with attendant known sequelae, need to be further evaluated and confirmed in future studies.