Mandibular repositioning splints (MRSs) and continuous positive airway pressure (CPAP) are used to treat the sleep apnea/hypopnea syndrome (SAHS). There are some data suggesting that patients with milder symptoms prefer MRS, but there are few comparative data on outcomes. Therefore, we performed a randomized crossover trial of 8 weeks of CPAP and 8 weeks of MRS treatment in consecutive new outpatients diagnosed with SAHS (apnea/hypopnea index [AHI] >or= 5/hour, and >or= 2 symptoms including sleepiness). Assessments at the end of both limbs comprised home sleep study, subjective ratings of treatment value, sleepiness, symptoms, and well-being, and objective tests of sleepiness and cognition. Forty-eight of 51 recruited patients completed the trial (12 women; age [mean +/- SD], 46 +/- 9 years; Epworth 14 +/- 4; median AHI, 22/hour; interquartile ratio [IQR], 11-43/hour). Significant (p <or= 0.01) differences between MRS and CPAP were observed for 7 of 21 variables (effect sizes, 0.3-0.6 SDs), all favoring CPAP, including AHI (15 +/- 16 and 8 +/- 6/hour, respectively), effectiveness rating, symptoms, Epworth (12 +/- 5 and 8 +/- 5, respectively), functional outcomes of sleepiness questionnaire, short-form 36 health survey mental component, and health transition scores. Objective sleepiness, cognitive performance, and preference for treatments were not different. In patients experiencing a mild form of the syndrome (AHI < 15, n = 18), symptoms, treatment efficacy and satisfaction, and subjective sleepiness were also better with CPAP than with MRS (effect sizes, 0.7-1.1 SDs). These results do not support these MRS devices as first-line treatment for sleepy patients with SAHS.