Introduction: In adult patients with epilepsy, treatment of comorbid obstructive sleep apnea syndrome (OSAS) by positive airway pressure (PAP) therapy results in improvements in the control of seizures. This is the first study investigating the long-term compliance with PAP therapy in patients with sleep-related epilepsy and OSAS. Methods: In this longitudinal study, patients with sleep-related epilepsy and OSAS were followed-up for five years. The compliance with PAP therapy was defined as the use of PAP therapy for at least four hours per night for more than 70 % of nights. Results: A total of 58 patients with sleep-related epilepsy and OSAS completed study protocol. Eleven patients (19.0 %) refused PAP treatment for OSAS, and 13 patients (22.3 %) showed irregular use. Remaining 34 patients (58.7 %) were compliant with PAP therapy. Females were found to be more compliant than males (p = 0.027), while the age was not found to correlate with the compliance (p = 0.721). Epilepsy-related factors including the types of seizures, whether pure sleep-related or mixed (p = 0.403), localization (p = 0.920) or lateralization (p = 0.697) of discharges, showed no effect on the compliance with PAP therapy. On the other hand, patients with a lower number of seizures (p = 0.042) or with a lower seizure frequency (p = 0.048) showed better compliance with PAP therapy. Polysomnographic parameters including severity of OSAS failed to show a significant correlation. Conclusion: Our findings showed that about two thirds of the study population was compliant with PAP therapy after a mean follow-up duration of almost three years. Newly-diagnosed patients, mostly females, with a lower number of total seizures and lower seizure frequency seem to be more compliant with PAP therapy, which implies the significance of investigation and treatment of OSAS as early as possible in the patients with sleep related seizures.