Purpose: Information on access and adherence to positive airway pressure (PAP) treatment is lacking at the regional level in Latin America. This study characterized access and adherence to PAP in patients with moderate-severe obstructive sleep apnea (OSA) in Latin America. Methods: Cross-sectional study, conducted at 9 sleep centers across Argentina, Brazil, Chile, Colombia, Mexico, and Peru. Adults diagnosed with moderate-severe OSA (apnea-hypopnea index [AHI] ≥ 15/h) in the previous 12–18 months were eligible. Anthropometrics, health coverage, and OSA severity data were collected. Data on access to therapy, barriers to access, adherence, and factors related to non-compliance were obtained via standardized telephone survey. Results: Eight hundred eighty patients (70% male, 54 ± 13 years, AHI 49 ± 28/h, body mass index 32 ± 7 kg/m2) were included. Four hundred ninety patients (56%) initiated PAP, 70 (14%) discontinued therapy during the first year (mainly due to intolerance), and 420 (48%) were still using PAP when surveyed. Health insurance was private in 36.9% of patients, via the social security system in 31.1%, and via the state in 13.3%, and 18.7% did not have any coverage; 49.5% of patients had to pay all equipment costs. Reasons for not starting PAP were unclear or absent indication (42%), coverage problems (36%), and lack of awareness of OSA burden (14%). Patients with better adherence were older (55.3 ± 13 vs 52 ± 13; p = 0.002) and had more severe OSA (AHI 51.8 ± 27 vs 45.6 ± 27; p = 0.001). Conclusions: Less than half moderate-severe OSA patients started and continue to use PAP. Unclear or absent medical indication and financial limitations were the most relevant factors limiting access to therapy.