Patients diagnosed with obstructive sleep apnea syndrome were randomly placed on automatic continuous positive airway pressure (ACPAP) for 2 hours followed by manual titration for the rest of the night. One hundred sixty-one patients entered the study, with at least 50 patients titrated with each of 3 ACPAP devices. The optimum continuous positive airway pressure (CPAP) was defined as the lowest pressure with an apnea-hypoxia index of ≤5/hr, which ranged from 4 cm to 18 cm. Success with ACPAP was approximately 60%-80% when the optimum CPAP was 4-6 cm but fell to below 30% if the optimum CPAP was ≥8 cm (P = 0.001). Average ACPAP ranged from 2 to 10 cm below the optimum level if the optimum CPAP was ≥8 cm. Patients who responded to a low CPAP but deteriorated on higher pressures failed to respond to any of the automatic devices. We recommend that CPAP titration be performed manually before initiation of ACPAP in patients with obstructive sleep apnea. The basal pressure for ACPAP should be the optimum pressure obtained by manual titration. Limits on the upper level of ACPAP may be necessary for patients who deteriorate on higher positive pressures.