We tested the hypothesis that structured epilepsy nursing improves quality of life (QOL). One hundred fourteen adult patients with uncontrolled epilepsy were randomly assigned to either an intervention group or a control group. The intervention group was offered an interactive, 1-day group education program followed by extended nurse follow-up and counseling. The nurse was present at as many outpatient consultations as possible and performed repeated consultations by telephone. All patients completed the QOLIE-89 before randomization and after 2 years. QOL was significantly improved from inclusion to completion of study in the intervention group (P=0.019), mainly in the subitems for Health Discouragement (P=0.01), Medication Effects (P=0.035), and Physical Role Limitations (P=0.05). To our knowledge, this is the first study to demonstrate a significant effect of a structured nurse-led intervention program in QOL of patients with epilepsy.