This study explored changes over time and in the internal standards of the quality of life, prolonged grief and family strain of informal caregivers of patients in vegetative state. Data obtained from 52 caregivers showed high levels of prolonged grief and family strain, and low quality of life. A decrease of caregivers’ quality of life and an increase of family strain were found by adopting a response shift procedure. Only prolonged grief did not change during time. Clinical intervention with the caregivers of vegetative state patients should be differentiated on the basis of the duration of the caring experience.