Background: CPAP is the first-line therapy for OSA. A high or variable residual apnea-hypopnea index (rAHI) reflects treatment failure and potentially is triggered by exacerbation of cardiovascular comorbidities. Previous studies showed that high rAHI and large rAHI variability are associated with underlying comorbidities, OSA characteristics at diagnosis, and CPAP equipment, including mask type and settings. Research question: What factors are associated with predefined groups with low to high rAHI variability? Study design and methods: This registry-based study included patients with a diagnosis of OSA who were receiving CPAP treatment with at least 90 days of CPAP remote monitoring. We applied the hidden Markov model to analyze the day-to-day trajectories of rAHI variability using telemonitoring data. An ordinal logistic regression analysis identified factors associated with a risk of having a higher and more variable rAHI with CPAP treatment. Results: The 1,126 included patients were middle-aged (median age, 66 years; interquartile range [IQR], 57-73 years), predominantly male (n = 791 [70.3%]), and obese (median BMI, 30.6 kg/m2 (IQR, 26.8-35.2 kg/m2). Three distinct groups of rAHI trajectories were identified using hidden Markov modeling: low rAHI variability (n = 393 [35%]), moderate rAHI variability group (n = 420 [37%]), and high rAHI variability group (n = 313 [28%]). In multivariate analysis, factors associated with high rAHI variability were age, OSA severity at diagnosis, heart failure, opioids and alcohol consumption, mental and behavioral disorders, transient ischemic attack and stroke, an oronasal mask, and level of leaks when using CPAP. Interpretation: Identifying phenotypic traits and factors associated with high rAHI variability will allow early intervention and the development of personalized follow-up pathways for CPAP treatment.