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Background: The majority of care for older adults with multiple chronic conditions (MCC) is provided by family (including friends) caregivers. Although caregivers have reported positive benefits to caregiving they also experience decreases in their physical and mental health. As there is a critical need for supportive interventions for this population, it is important to know what influences the health of family caregivers of persons with MCC. This research examined relationships among the changes from baseline to 6 months in health related quality of life (SF12v2) of family caregivers caring for older adults with multiple chronic conditions and the following factors: a) demographic variables, b) gender identity [Bem Sex Role Inventory (BSRI)] c) changes in general self-efficacy [General Self Efficacy Scale (GSES) (baseline to 6 months) and d)) changes in caregiver burden [Zarit Burden Inventory (ZBI)] baseline to 6 months. Specific hypothesis were based on a conceptual framework generated from a literature review., Methods: This is a secondary analysis of a study of 194 family caregivers who were recruited from two Canadian provinces Alberta and Ontario. Data were collected in-person, by telephone, by Skype or by mail at two time periods spaced 6 months apart. The sample size for this secondary analysis was n = 185, as 9 participants had dropped out of the study at 6 months. Changes in the scores between the two time periods were calculated for SF12v2 physical component score (PCS) and mental component score (MCS) and the other main variables. Generalized Linear Modeling was then used to determine factors associated with changes in HRQL., Results: Participants who had significantly positive increases in their MCS (baseline to 6 months) reported lower burden (ZBI, p < 0.001), and higher general self-efficacy (GSES, p < 0.001) and Masculine BSRI (p = 0.025). There were no significant associations among variables and changes in PCS (baseline to 6 months)., Conclusions: Our findings suggest that a masculine gender identity (which incorporates assertive and instrumental approaches to caregiving), and confidence in the ability to deal with difficult situations was positively related to improvement in mental health for caregivers of persons with MCC. Decreases in perceptions of burden in this populations was also associated with improvements in mental health. Further research is needed to explore ways to support caregivers of older persons with multiple chronic conditions living at home.