Temporal lobectomy appears to be an effective treatment for medically intractable epilepsy. However, the influences of pre-operative health status and post-operative reductions in seizure activity on post-surgical health-related quality of life (HRQOL) are not well understood. We used the Epilepsy Surgery Inventory 55 (ESI-55) to evaluate changes between pre- and post-operative HRQOL in 47 temporal lobectomy patients. Patients exhibited significantly improved scores in five HRQOL domains: health perceptions; energy fatigue; social function; cognitive function and role limitations due to physical problems. Although significant improvements in HRQOL were observed, this was not the case for all patients. Specifically, patients with low or medium pre-operative HRQOL scores were found to have the greatest degree of improvement post-operatively. Patients with high pre-operative scores did not exhibit these same improvements, although they continued to report high scores. The results indicate that the ESI-55 is a satisfactory instrument to measure change in HRQOL but also emphasizes that the magnitude of change in post-operative HRQOL scores tends to vary according to baseline scores. The outcome of temporal lobectomy is not entirely based upon the procedure's ability to reduce the frequency of seizures, but is also influenced by level of HRQOL prior to surgery.