Whether computerized autoadjusted continuous positive airway pressure (aCPAP) is effective or even superior to constant continuous positive airway pressure (cCPAP) in the treatment of obstructive sleep apnea syndrome (OSAS) is still controversial. We performed a randomized, double-blind, controlled, cross-over trial comparing efficacy of sleep apnea home therapy by a novel aCPAP machine (REMStarAuto; Respironics; Murrysville, PA) operated in autoadjusted or constant mode. Thirty sleep apnea patients were recruited consecutively. Mean baseline Epworth sleepiness scale (ESS) score was 12.7 ± 0.6 (± SD), mean sleep resistance time was 26 ± 2 min (Osler test; Stowood Scientific Systems; Oxford, UK), and mean apnea-hypopnea index (AHI) was 41.1 ± 3.6 h. Patients were randomly assigned to 1 month of home therapy with aCPAP followed by 1 month with cCPAP, or vice versa. After 1 month with treatment, the mean ESS score, sleep resistance time, and AHI were significantly improved (6.6 ± 0.6, 37 ± 1 min, and 4.6 ± 0.7 h, respectively; all p < 0.05 vs baseline). Similar effects were achieved with cCPAP (p = not significant vs aCPAP). Twenty-six patients preferred aCPAP, and 4 patients preferred cCPAP (p < 0.001). We conclude that patients with OSAS preferred aCPAP over cCPAP in the initial phase of therapy. The effectiveness aCPAP in improving major outcomes was equivalent to cCPAP. Since aCPAP does not require initial titration, it is a simple and promising modality for sleep apnea home therapy.