OBJECTIVE: The main purpose of this study was to determine the occurrence of primary headaches between seizures in patients with epilepsy. The specific aim was to determine the influence of antiepileptic therapy on the frequency of interictal headaches and on the quality of life of patients with epilepsy. STUDY DESIGN: The research is organized as a prospective cross-sectional study. PARTICIPANTS AND METHODS: The research included thirty patients with epilepsy who are using antiepileptic therapy and are treated at the Department for epilepsy, the Clinic of Neurology at the Osijek University Medical Center. The instruments used as research tools were an anonymous questionnaire structured for the purposes of this research, which was applied to collect data on the demographic characteristics of the patients and data on clinical variables related to epilepsy and headache, and the Short Form 36 Health Survey (SF-36). RESULTS: Out of thirty patients with epilepsy and headaches included in this study, 90 % have interictal and 10 % periictal headache. The incidence of headaches was reduced in 16 (53 %) respondents after initiating antiepileptic therapy. The majority of respondents (90%) are treated with antiepileptic monotherapy. The quality of life in respect of both physical and mental health does not differ whether antiepileptic monotherapy or polytherapy is applied. CONCLUSION: Headaches in patients with epilepsy are mostly interictal, and antiepileptic drugs do not significantly affect the frequency, duration, and intensity of headaches. The quality of life does not differ considerably depending on the number of antiepileptics used.