The Quality of Life after Brain Injury (QoLIBRI) questionnaire was developed and validated to assess disease-specific health-related quality of life (HRQoL) in individuals after TBI. The present study aims to determine its longitudinal validity by assessing its responsiveness and response shift from 3 to 6 months post-injury. Analyses were based on data from the European longitudinal observational cohort Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury study. A total of 1659 individuals recovering from TBI were included in the analyses. Response shift was assessed using longitudinal measurement invariance testing within the confirmatory factor analyses framework. Responsiveness was analyzed using linear regression models that compared changes in functional recovery as measured by the Glasgow Outcome Scale–Extended (GOSE) with changes in the QoLIBRI scales from 3 to 6 months post-injury. Longitudinal tests of measurement invariance and analyses of discrepancies in practical significance indicated the absence of response shift. Changes in functional recovery status from three to six months were significantly associated with the responsiveness of the QoLIBRI scales over the same time period. The QoLIBRI can be used in longitudinal studies and is responsive to changes in an individual’s functional recovery during the first 6 months after TBI.