RATIONALE: How to provide advanced respiratory support for COVID-19 to maximize population-level survival while optimizing mechanical ventilator access is unknown. OBJECTIVES: To evaluate the use of high-flow nasal cannula for COVID-19 on population-level mortality and ventilator availability. METHODS: We constructed dynamical (deterministic) simulation models of high-flow nasal cannula and mechanical ventilation use for COVID-19 in the U.S. Model parameters were estimated through consensus based on published literature, local data, and experience. We had two outcomes: (1) cumulative number of deaths and (2) days without any available ventilators. We assessed the impact of various policies for use of high-flow nasal cannula (with or without "early intubation") versus a scenario where high-flow was unavailable. RESULTS: The policy associated with the fewest deaths and the least time without available ventilators combined the use of high-flow nasal cannula for patients not urgently needing ventilators with the use of early mechanical ventilation for these patients when at least 10% ventilator supply was not in use. At the national level, this strategy resulted in 10,000 - 40,000 fewer deaths than if high-flow nasal cannula were not available. Additionally, with moderate national ventilator capacity (30,000-45,000 ventilators), this strategy led to up to 25 (11.8%) fewer days without available ventilators. For a 250-bed hospital with 100 mechanical ventilators, the availability of 13, 20, or 33 high-flow nasal cannulas prevented 81, 102, and 130 deaths, respectively. CONCLUSIONS: Use of high-flow nasal cannula coupled with early mechanical ventilation when supply is sufficient results in fewer deaths and greater ventilator availability.