OBJECTIVES: To assess the effect of brivaracetam (BRV), a new adjunctive therapy of partial-onset seizures (POS), on health-related quality of life (HRQoL). METHODS: Data from three previously reported Phase III trials of BRV in adults with refractory POS (NCT00490035; NCT00464269; NCT01261325) were pooled. The QOLIE-31-P was collected at randomization and after the 12-week treatment period or early termination. The QOLIE-31-P is an epilepsy-specific instrument with seven subscales and a Total score ranging from 0 (worse) to 100 (better HRQoL). Mean change from baseline to last observation was compared between BRV and placebo using ANCOVA controlling for baseline score. Percentages of meaningfully improved patients were calculated using published thresholds. RESULTS: There were 422, 179, 324, and 235 patients in the placebo, BRV 50mg/day, 100mg/day, and 200mg/day groups respectively. All mean (SD) changes were positive; they were similar for placebo and BRV for the Total score (+2.8 [12.7], +3.0 [14.0], +2.4 [14.0], +3.0 [12.1]) and most subscale scores. There was a BRV dose response for Energy/Fatigue (lower scores), Daily Activities and Seizure Worry (both higher scores). BRV 100mg/day showed significantly larger improvements than placebo (+7.3 [24.6] vs +5.0 [23.1]; p=0.044) on the Seizure Worry subscale; this was the only significant result. 43.6%, 41.7%, and 36.6% of BRV 50mg/day, BRV 100mg/day, 200mg/day patients experienced a meaningful improvement in the Total score, respectively; the rate was 38.6% for placebo. CONCLUSIONS: Changes in HRQoL were small and generally comparable between treatment groups. Differences reflected the known efficacy and safety profile of BRV. Where reported for other AEDs, changes from baseline and treatment group differences are similarly small, raising questions about the appropriateness of short-term fixed-dose trials as a source of HRQoL data for adjunctive AEDs in refractory patients. Long-term assessments may be more informative. Supported by UCB.