We conducted a prospective study over 24 months to compare health-related quality of life in surgically and medically treated patients with intractable temporal lobe epilepsy. Seizure frequency and health-related quality of life were assessed in 81 patients before and 6, 12, and 24 months after treatment. Using the Epilepsy Surgery Inventory 55 (ESI-55), we compared (1) different seizure outcome groups and (2) temporal lobectomy with continuing medical management. Follow-up was satisfactory in 72 patients (89%), 51 treated with temporal lobectomy and 21 with no surgery. Pretreatment seizures and health-related quality of life were comparable in the two groups. Seizure outcome was significantly better at 6, 12, and 24 months after surgery. At 24 months, seizure-free patients and those with at least a 90% reduction in seizure frequency reported significant improvements in health-related quality of life (on 5 of 10 subscales and overall Epilepsy Surgery Inventory 55 scale). Deterioration in quality of life occurred with less than 90% seizure reduction. Only one Epilepsy Surgery Inventory 55 subscale at 6 months and two subscales at 12 months showed a significant difference. Patients with good seizure outcome experience improved health-related quality of life after treatment. Since temporal lobectomy results in considerably better seizure control than continued medical management, the findings support surgery as the preferred treatment, although changes in health-related quality of life may not be evident until the second postoperative year.