Background: Patients with epilepsy and their families require general and specialized health education about the condition to enable them to make decisions to minimize the impact of epilepsy on their lives. The provision of good quality, relevant education about the condition is one of the most important roles that the nurse should undertake. This work aimed to determine the effect of health education program on self-management practices and quality of life in patients with epilepsy. Method: This quasi-experimental design was carried out on 80 patients aged from 20 to 60 years old, diagnosed with epilepsy for at least one year. Patients were divided into two equal groups. The study group subjected to the designed health education program in addition to the routine hospital care. The control group received the routine epilepsy care offered by their clinic, which is brief history taking, prescribing of antiepileptic drugs, and asking laboratory investigations as needed. Results: There was a highly statistically significant positive correlation between the mean percent score of knowledge and epilepsy self-management practices and quality of life in epilepsy inventory (QOLIE) overall score among the study group one month and three months post implementation of the health education program. There was a highly statistically significant positive correlation between the mean percent score of epilepsy self-management practices and QOLIE overall score among the study group at one month and three months after the health education program. Conclusion: Adult patients with epilepsy who receive health education exhibit higher knowledge, self-management practices and mean scores than those patients who did not receive.