Purpose: Positive airway pressure (PAP) devices have been widely used as the first line of treatment in obstructive sleep apnea (OSA). Most advanced PAP devices support the estimation of respiratory index (RI) using the patient’s mask airflow. In addition to the compliance factor for PAP device use, which is important for monitoring patient sleep health, RI is also becoming important for monitoring. However, there are few reports that validate RI of a PAP device with polysomnography. Methods: Between January 2015 and December 2017, 50 participants were enrolled who were diagnosed with OSA and prescribed auto-titration PAP (APAP) devices. The RIs of participants were measured at night using APAP devices, concurrently with electroencephalography, respiratory inductance plethysmography sensors, and other polysomnographic sensors in a sleep laboratory. The respiratory-related data of APAP were prospectively analyzed with the manually scored polysomnographic data. Results: The apnea-hypopnea index and apnea index showed a statistically close relationship between the auto-scored respiratory data from the APAP device and the manually scored respiratory data from polysomnographic sensors. Obstructive apnea and central apnea indices showed relatively low correlations. The differences between the auto-scored RI and manually scored RI were influenced by BMI, waist circumference, weight, oxygen saturation, and respiratory distress indices of diagnostic polysomnographic factors. Conclusions: The RIs of APAP devices have a tendency to be underestimated or mismatched when compared with polysomnography. Sleep specialists are advised to consider additional anthropometric and diagnostic factors to account for these differences during PAP treatment.