Study Objectives: Despite the overall improvement in posttraumatic stress disorder (PTSD) symptomatology with continuous positive airway pressure (CPAP) therapy, adherence to CPAP is far worse in veterans with PTSD compared to the general population with obstructive sleep apnea (OSA). The aim of this study was to compare the efficacy, adherence, and preference of CPAP versus mandibular advancement device (MAD) and the effect of these treatments on health outcomes in veterans with PTSD. Methods: Forty-two subjects with PTSD and newly diagnosed OSA by polysomnography were treated in a randomized, crossover trial of 12 weeks with CPAP alternating with MAD separated by a 2-week washout period. The primary outcome was the difference in titration residual apnea-hypopnea index (AHI) between CPAP and MAD. Secondary outcome measures included PTSD Checklist and health-related quality of life (Medical Outcomes Study 36-Item Short Form and Pittsburgh Sleep Quality Index). Results: Analyses were limited to the 35 subjects (mean age 52.7 ± 11.6 years) who completed the trial, regardless of compliance with their assigned treatment. CPAP was more efficacious in reducing AHI and improving nocturnal oxygenation than MAD (P < .001 and P = .04, respectively). Both treatments reduced PTSD severity and ameliorated scores of the Medical Outcomes Study Short Form 36 and Pittsburgh Sleep Quality Index, although no differences were detected between the CPAP and MAD arms. The reported adherence to MAD was significantly higher than CPAP (P < .001), with 58% preferring MAD to CPAP. Conclusions: Although CPAP is more efficacious than MAD at improving sleep apnea, both treatment modalities imparted comparable benefits for veterans with PTSD in relation to PTSD severity and health-related quality of life. 1 Veterans having PTSD suffer from nonrestorative sleep and nightmares leading to heightened state of arousal and anxiety, increased severity of depression, and poor quality of life.2 Accruing evidence suggests that patients with PTSD are at higher risk for sleep-disordered breathing than the general population.3,4 In a series of studies looking at postdeployment combat veterans with PTSD, rates of overall sleep disturbance symptoms approached 90%, with up to 70% considered to be at high risk for OSA. and substance abuse. BRIEF SUMMARYCurrent Knowledge/Study Rationale: In veterans with posttraumatic stress disorder (PTSD), the disturbed sleep can worsen the cognitive-behavioral manifestations of PTSD and contribute to poor mental and physical health outcomes. Because adherence to treatment with CPAP is less than optimal in this population, this study was undertaken to examine the clinical efficacy, compliance, and quality of sleep of mandibular advancement devices (MAD) compared to CPAP in veterans with OSA and PTSD. Study Impact: Although CPAP is more efficacious in eliminating respiratory events, both MAD and CPAP result in similar beneficial changes in daytime sleepiness, PTSD symptomatology, and healthrelated quality of life measures in v...