Purpose <p>To investigate the real-world status of continuous positive airway pressure (CPAP) persistence in patients with sleep apnea syndrome (SAS) using administrative claims data in Japan.</p> Methods <p>We designed a retrospective longitudinal study using administrative claims and medical check-up data collected from April 2014 to February 2022. We identified patients newly starting CPAP therapy as their first-line SAS treatment, and assessed patient characteristics, CPAP persistence rates, predictors of CPAP discontinuation, and second-line therapy options.</p> Results <p>The analysis population (<i>n</i> = 13,007) was 76.2% male, and the mean age (± standard deviation) was 64.0 ± 15.0 years. CPAP persistence rates were 90.1% at 90 days, 77.1% at one year, 70.3% at two years, and 66.5% at three years. More discontinuation was noted in patients aged 18 to 44 (adjusted hazard ratio [95% confidence interval]: 1.27 [1.13–1.42]) and ≥ 65 (65–74 years, 1.18 [1.07–1.30]; ≥75 years, 1.59 [1.43–1.76]) than in those aged 45 to 64. Comorbidities of dementia (1.47 [1.25–1.73]), insomnia (1.26 [1.16–1.36]), and restless legs syndrome (RLS, 1.60 [1.16–2.23]) were also associated with more discontinuation. Testing with a Type 3 portable monitor (1.31 [1.21–1.42]), or no record of sleep testing before therapy (1.21 [1.09–1.36]), tended to be associated with more discontinuation than polysomnography. CPAP therapy starting in 2020 (0.72 [0.63–0.82]) and 2021 (0.63 [0.46–0.85]) resulted in better persistence than that starting in 2016. Only 6.1% of patients received second-line therapy after CPAP discontinuation.</p> Conclusions <p>CPAP therapy was continued for at least a year by about 80% of patients. Because second-line therapies are rarely implemented, efforts are needed to ensure CPAP persistence by considering the factors that influence it. It is also crucial to raise awareness of alternative therapies.</p> Registration number <p>NA.</p>