Purpose <p>Residual respiratory events (RREs) are common in continuous positive airway pressure (CPAP) users. They can lead to poor CPAP adherence and early termination. The management of RREs has not been standardized yet. The purpose of this study was to test a structured management algorithm for RREs detected by CPAP devices in OSA patients.</p> Methods <p>This was a prospective observational clinical study that aimed to test a specific algorithm in patients exhibiting RREs. This study also included a case-control comparison. Cases were OSA patients (AHI <i>≥</i> 15) exhibiting RREs (AHI_flow &gt;10) during the first 3 months of CPAP use, reported by telemonitoring. The control group were similar CPAP patients with no RREs. All underwent in-lab polysomnography (PSG) with manual titration to set the fixed CPAP pressure on the Resmed^® CPAP device. In case of RRE, a specific algorithm was followed to manage and resolve these events, applied only after leak correction.</p> Results <p>A total of 19/273 patients exhibited RREs. Compared to matched controls, cases had higher RREs on titration PSG and used more often naso-buccal masks (<i>p</i> &lt; 0.05). Among the 19 RRE patients, predominant obstructive AHI_flow was observed in 15 patients, which generally resolved rapidly with an increase in CPAP pressure, allowing an AHI_flow <i>≤</i>10 to be obtained. Predominant central AHI_flow and Cheyne-Stokes respiration (CSR) was observed in four patients. Individualized management was successful and one was moved to auto-servo ventilation.</p> Conclusions <p>Once leaks are controlled, occurrence of RREs in compliant CPAP users is uncommon. A structured algorithm helped clarify the likely mechanism of device-detected RREs and guided individualized management during the first months of CPAP therapy. The most common cause of RRE was insufficient CPAP pressure, but cases of COMISA and of “idiopathic” central sleep apnea (CSA)/CSR also occurred that required specific management.</p>