Objective: To evaluate the short-term (3 months) effects of family nursing therapeutic conversations (FNTC) on health-related quality of life, self-care and depression in outpatients with Heart failure (HF). Methods: A randomised multi-centre trial was conducted in three Danish HF clinics. The control group (n = 167) received usual care, and the intervention group (n = 180) received FNTCs as supplement to usual care. Primary outcome was clinically significant changes (6 points) in Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score between groups. Secondary outcomes were changes in self-care behaviour and depression scores. Data were assessed before first consultation and repeated after three months. Results: No statistically significant difference was found in the change of KCCQ, self-care and depression scores between the groups. KCCQ scores of patients in the FNTC group changed clinically significant in seven domains, compared to one domain in the control group, with the highest improvement in self-efficacy, social limitation and symptom burden. Conclusion: FNTC was not superior to standard care of patients with HF regarding health-related quality of life, self-care and depression. Implication for practice: Addressing the impact of the disease on the family, might improve self-efficacy, social limitation and symptom burden in patients with heart failure.