OBJECTIVES: Epilepsy and its treatment can have profound effects on the quality of life (QOL) of many patients, particularly those with seizures refractory to treatment. Detecting changes in QOL in trials of anti-epileptic drugs as add-on therapy over a short period is, however, known to be difficult. METHODS: In this study, we examined the relationship between patients’ perception of quality of life change, using QOL transition scales, and objective quality of life mean change scale scores, using the QOLIE-31, for similar constructs in a 3-month study of add-on therapy in 329 refractory epilepsy patients experiencing partial seizures. The validity and responsiveness of the QOL transition scales, the QOLIE-31 scales, compliance and treatment satisfaction scales were also examined. RESULTS: Correlations between the QOL transition scales and QOLIE-31, satisfaction and compliance mean change scores were significant but low to moderate (0.10–0.39) for the majority of scales. The QOLIE-31 worry scale and the treatment satisfaction scale proved to be the most responsive to clinical changes. The transition scales, however, often indicated that responders perceived significantly more improvement than non-responders, particularly for change in social life and global QOL. CONCLUSIONS: These results suggest that measuring patients’ perception of change in QOL is not the same as measuring change in QOL objectively (i.e. over time). Perceptions appear to play an important role in patients’ satisfaction with and willingness to continue treatment. In addition, patients’ perceptions of treatment and its effect on their lives appear sensitive to short-term treatment. These changes may, however, be distinct from those QOL domains that change with sustained control of seizures. Further research into patient satisfaction and perceptions of QOL change, particularly in short-term epilepsy trials, may be valuable in refining measurement methodology.