Background Providing care often causes negative reactions and psychological distress in family caregivers of patients with heart failure. How these 2 constructs are related has not been fully explored. Objective The aims of this study were to describe caregiver reactions to caregiving and psychological distress and to determine the associations between caregiver reactions to caregiving and psychological distress in family caregivers of patients with heart failure. Methods In this secondary analysis of a cross-sectional study, the sample included 231 patients and their family caregivers. The Chinese version of the Hospital Anxiety and Depression Scale was used to assess psychological distress (ie, symptoms of anxiety and depression), and the Caregiver Reaction Assessment was used to measure both negative and positive caregiver reactions to caregiving, including financial problems, impact on schedule, health problems, lack of family support, and self-esteem. Results Of the participants, 15.2% and 25.5% of caregivers reported symptoms of depression and anxiety, respectively. Impact on schedule was the most common caregiver reaction, followed by financial problems. Impact on schedule was related to both the caregivers' symptoms of depression (odds ratio [OR], 1.705; P = .001) and anxiety (OR, 1.306; P = .035), whereas financial problems were only related to symptoms of anxiety (OR, 1.273; P = .011). Conclusions The findings suggest that interventions for reducing the negative impact on schedule of caregiving and helping to solve the caregivers' financial concerns might help to relieve their symptoms of depression and anxiety.