Rationale: Clear definition of optimal positive airway pressure therapy usage in patients with obstructive sleep apnea is not possible due to scarce data on the relationship between usage hours and major clinical outcomes. Objective: To investigate the dose-response relationship between positive airway pressure usage and healthcare resource utilization, and determine the minimum device usage required for benefit. Methods: A linked data set combined de-identified payer-sourced administrative medical/pharmacy claims data from >100 US health plans and individual patient positive airway pressure usage data. Eligible adults (age ≥18 years) had a new obstructive sleep apnea diagnosis between June 2014 and April 2018. All received positive airway pressure therapy (AirSense™ 10; ResMed) with claims data for ≥1 year before, and 2 years after, device setup. Healthcare resource utilization was determined based on the number of all-cause hospitalizations and emergency room visits over 3, 12 and 24 months after positive airway pressure initiation. Results: Data from 179,188 patients showed a clear dose-response relationship between daily positive airway pressure usage and healthcare utilization. Minimum device usage required for benefit was 1-3 h/night. There was a statistically significant decrease in hospitalizations and ER visits at all time points (all p<0.0001) with increasing PAP usage. Each additional h/night of usage decreased hospitalizations/emergency room visits by 5-10%/5-7%. Conclusions: These data provide compelling evidence for a dose-response relationship between positive airway pressure usage and healthcare utilization, with benefits seen even when usage is as low as 1-2 h/night.