OBJECTIVES: Poorer health related quality of life (HRQOL) has been observed among dementia caregivers relative to the general population. However, the temporal stability of and factors associated with caregiver HRQOL have been little studied. METHODS: Dementia caregivers were randomized to one of two treatment arms: a multi-component, psychosocial intervention aimed at increasing social support (n=69) or to a usual care, control group (n=65). Caregiver HRQOL was assessed over a two-year period using a Visual Analogue Scale (VAS), the Health Utilities Index Mark III (HUI), and the SF-36 (physical health [PCS] and mental health [MCS] summary scores). Patient-specific and caregiver-specific data were collected every four-months during the first year and every six-months thereafter. A step-wise, mixed-model approach was employed to assess the association of treatment-, patient-, and caregiver-specific variables to caregiver HRQOL. RESULTS: None of the patient demographic variables was associated with caregiver HRQOL. Caregiver gender, health status and depression along with patient dementia severity were all inversely associated with the VAS, but patient nursing home placement was positively associated. Caregiver age, health status and depression were inversely associated with the HUI. Dementia severity and caregiver depression were inversely associated with the MCS. Caregiver age and health status were inversely associated with the PCS. Time since enrollment was positively associated with caregiver MCS but inversely associated with caregiver PCS; time was not significantly associated with the VAS or HUI. CONCLUSIONS: A number of patient-, caregiver-, and time-related variables were differentially associated with the disparate measures of HRQOL. Caregiver depression and health status are consistently associated with poorer HRQOL regardless of instrument used to measure it. The VAS and HUI appear to be more stable measures of HRQOL than the summary scores from the SF-36. However, small sample size and methodological limitations temper these findings.