In patients with epilepsy, improvement in seizure control with treatment of coexisting obstructive sleep apnea (OSA) has been reported, but there is lack of data on the effect of continuous positive airway pressure (CPAP) compliance on seizure control in these patients. We examined the variability in seizure frequency in patients who were CPAP compliant and those who were not CPAP compliant. We undertook a retrospective review of clinical and polysomnographic data of adult patients with OSA and epilepsy seen at the Boston University Medical Center Epilepsy and Sleep Clinics between 2000 and 2010. Data were reviewed for CPAP compliance and seizure frequency after at least 6 months of CPAP use. Only patients with no changes in antiepileptic drug regimens during CPAP trial were included. Of the 660 patients identified, 41 fulfilled inclusion criteria, of whom 28 were CPAP compliant and 13 were not CPAP compliant. In the compliant group, CPAP use led to decreased seizure frequency from 1.8 per month to 1 per month (p = 0.01). In the noncompliant group, no significant difference in seizure frequency was noted between baseline (2.1 per month) and at follow-up (1.8 per month, p = 0.36). Sixteen of 28 CPAP-compliant subjects were seizure free, whereas only 3 of 13 non-CPAP compliant subjects were seizure free [relative risk (RR) 1.54, p = 0.05]. Patients with epilepsy and OSA not compliant with CPAP treatment are at higher risk of seizures than are CPAP-compliant patients. To validate this observation, further prospective studies are warranted