Summary: Purpose: A prospective study to investigate health‐related quality of life (HRQOL) outcome in patients with temporal lobe epilepsy treated with anterior temporal lobectomy (ATL). Methods: The majority of the patients with medically refractory focal epilepsy had Quality of Life in Epilepsy‐89 (QOLIE‐89) assessment at the time of prolonged video/EEG monitoring as part of their presurgical evaluation. Thirty‐seven patients who were not treated surgically constituted the control group, and 53 patients who underwent ATL made up the surgery group. Both control and surgery groups had HRQOL assessment repeated at ∼1‐ and 2‐year intervals. Repeated measures analysis of variance (ANOVA) was used to test for differences between the two groups. Results: For the overall score and almost every scale, the surgery group had a higher baseline mean than the control group. Because of this baseline difference, change scores were used in further analysis. The overall score and 10 of 17 scales in QOLIE‐89 showed significant HRQOL improvement after ATL, and the improvement was significant relative to score changes of the nonsurgical comparison group. Scores improved in overall QOL, emotional well‐being, attention/concentration, language, social isolation, health perception, role limitations‐physical, work/drive/social, health discouragement, and seizure worry. For the first five scales, there was group‐time interaction; the improvement was significantly more on the 2‐year than on the 1‐year follow‐up. When the surgery patients were divided into four categories (class IA‐, completely seizure free; class IA+, seizure free with aura; class II, rare seizures; class III, worthwhile improvement in seizure control; and class IV, no improvement), the improved HRQOL in the surgery group was almost entirely contributed by the class IA‐ outcome patients who were totally seizure free. The class IA+ patients with continuing aurae and class II/III/IV patients had no significant improvement in their overall HRQOL scores at 1‐ or 2‐year follow‐up. Conclusions: Overall score and 10 of the 17 scales of QOLIE‐89 significantly improved in patients with medically refractory temporal lobe epilepsy after ATL. For some scales, there was delay in the improvement to manifest. The HRQOL improvement was related to achieving an entirely seizure‐free status (i.e., no seizures or aurae postoperatively).