BACKGROUND: Treatment-emergent central sleep apnea (TECSA, formerly known as complex sleep apnea) is the conversion of obstructive sleep apnea (OSA) to central sleep apnea (CSA) and/or hypopnea while undergoing treatment, especially continuous positive air pressure (CPAP) therapy. Some research suggests prevalence of TECSA on CPAP could be as high as 20.3%, while other data reports prevalence as low as 0.56%. OBJECTIVES: The objective of this study is to elucidate the prevalence, as well as natural course, of TECSA with CPAP use which currently varies widely in different studies. METHODS: This is a prospective multicenter longitudinal study to be conducted with 3276 treatment-naïve OSA patients for 36 months each under a rolling enrollment model, with an estimated study run time of 5-6 years. After undergoing full-night CPAP titration, each patient will begin CPAP therapy at home using AirView or other ResMed PAP devices, which will record apnea-hypopnea index (AHI) and central apnea index (CAI) data into a U.S. PAP device telemonitoring database. Every six months, all patients will have a follow-up appointment, and a subset will receive full-night diagnostic polysomnography to confirm CPAP data. Patients will also self-assess and report habitual daytime sleepiness using the Epworth Sleepiness Scale upon diagnosis and at follow-up every 6 months. RESULTS: Prevalence of TECSA will be assessed for statistical significance using the Chi-squared test or Fisher’s exact test if expected cell counts are <5. Statistical significance is assumed for type I error <0.05. To measure the sensitivity and specificity of telemonitoring CPAP data, continuous variables for the accuracy and precision of the overlapping measures (AHI, apnea index, and hypopnea index) will be compared to PSG. Results from the Epsworth Sleepiness Scale will be measured by computing the mean score at each 6-month follow-up. DISCUSSION: This study will provide evidence as to the true prevalence of TECSA in the U.S. for OSA patients receiving CPAP therapy. Estimated TECSA prevalence while on CPAP therapy is anticipated to be higher than is currently shown in the literature, with a conservative estimate of 15%. As the largest study evaluating for TECSA prevalence to date, any results that are found will be more accurate than previous studies. This is expected to guide future treatment of OSA as a higher prevalence of TECSA while on CPAP therapy (the mainstay of OSA treatment) may impact clinical decision-making when considering treatment options for OSA.