The high cost of in-laboratory sleep studies and the insufficiency of available nights in most sleep laboratories has prompted clinical trials in an attempt to find an effective and safe method for continuous positive airway pressure (CPAP) titration in the unsupervised home environment. Earlier publications focused on the effectiveness of this new method but did not indicate the potential hazard and the selection criteria of patients. We accomplished a prospective study to evaluate a machine-controlled CPAP titration method in an unselected group of 21 patients with obstructive sleep apnea (OSA) requiring CPAP therapy. Unattended CPAP titrations were completed in the sleep laboratory, followed by conventional CPAP titration night. The CPAP levels assessed through automatic titrations showed strong agreement with those from the control nights. Fifteen patients had no pathologic cardiorespiratory events during machine-controlled titration. Undesirable cardiorespiratory complications developed in six patients with underlying cardiorespiratory disorder. Two patients had to stop the procedure. Two patients needed a reset of the actual pressure to baseline because of central apneas and one patient because of high-grade arrhythmia. The machine-controlled CPAP titration enabled reliable assessment of an effective pressure and appeared to be safe in selected patients with OSA. However, because the method caused significant adverse effects in some patients, we recommend that unattended CPAP titration not be attempted in patients with underlying cardiorespiratory disease.