We evaluated the efficacy of two different continuous positive airway pressure devices with automatic mask pressure adjustment (autoCPAP) in comparison with fixed CPAP in treating obstructive sleep apnea syndrome in 29 patients. The mean (+/- SE) apnea-hypopnea index was 46 +/- 4 per hour and the Epworth score was 14.2 +/- 0.7. Patients were treated over three consecutive 1-month periods with three regimens in random order: an autoCPAP device responding to apnea-hypopnea and snoring, another autoCPAP device responding to snoring and changes in flow contour, and fixed CPAP at the 90th pressure percentile titrated by autoCPAP over 2 weeks. Allowed pressure in the autoCPAP mode was 4 to 15 cm H2O. At the end of each treatment period, symptoms, quality of life, vigilance, and nocturnal breathing disturbances were evaluated. All three treatment modalities improved symptoms, quality-of-life domains, and apnea-hypopnea index significantly and to a similar degree. Mean (+/- SE) maintenance-of-wakefulness time increased by 4.5 +/- 1.8, 6.0 +/- 1.5, and 6.1 +/- 1.4 minutes with DeVilbiss AutoAdjust LT, AutoSet T, and fixed-pressure CPAP, respectively (p<0.001 vs. baseline, p=not significant for comparisons among the three modalities). We conclude that both autoCPAP devices were equally effective as fixed-pressure CPAP in improving major outcomes during short-term therapy of sleep apnea.