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The aim of this study was to investigate the quality of life (QOL) and to identify the factors (characteristics of patients and caregivers, caregiver burden, self-efficacy, and social support) related to QOL among family caregivers of patients with heart failure (HF) in Southwest China.The study had a cross-sectional descriptive design.Patients and their family caregiver dyads (N = 251) in three hospitals in Chengdu were recruited from April 2013 to September 2014. Data were collected by in-person interviews. Multivariate analyses were used to identify the factors associated with physical and mental QOL of caregivers.The median scores of physical and mental QOL were 70 and 60, respectively. Multivariate analysis demonstrated that higher New York Heart Association (NYHA) classification, more caregiving hours per day, more readmissions in the last 6 months, higher caregiver burden, and lower social support were associated with poorer physical and mental QOL. Lower self-efficacy was also associated with poorer physical QOL. The variances of physical (73%) and mental (70%) QOL of caregivers were explained by these identified significant factors.The caregivers of patients with HF in Southwest China had perceived reduced QOL and experienced more seriously impaired mental health than physical health.Early assessments, strategies, and policy supports developed particularly for caregivers in undeveloped areas are necessary to identify caregivers who are at a high risk of reduced QOL and to improve their well-being.