Partners of patients with heart failure provide both practical and emotional support. Many partners assume caregiving responsibilities without being aware of the burden related with this role. Our work has established that a psycho-educational intervention has benefits at 3, but not at 12 months for patients with heart failure. Further we had not described the long-term effects in caregivers. This study aimed to determine the 24-months effects of a dyadic psycho-educational intervention on caregiver burden and morbidity in partners of patients with heart failure and study factors associated with a change in caregiver burden. A randomized controlled study design, with a follow-up assessment after 24 months. Partners to patients with heart failure were recruited from two hospitals in the southeast of Sweden. A three session nurse-led psycho-educational program was tested and included psychosocial support to maintain the partners' physical and mental functions, and perceived control. Several instrument were used to measure caregiver burden, perceived control, physical and mental health, depression and morbidity. One hundred fifty-five partners were included. There were no significant differences in any index of caregiver burden or morbidity among the partners in the intervention and control groups after 24 months. Overall, the mean total caregiver burden was found to be significantly increased compared to baseline (36 +/- 12 vs 38 +/- 14, p < 0.05). A younger partner, less comorbidity, higher levels of perceived control, better physical health and less symptoms of depression in patients, and better mental health in the partners were factors associated with absence of increased caregiver burden over time. Our intervention did not significantly decrease caregiver burden or morbidity. Over time, several aspects of burden increased in both groups. To improve outcomes, individualized and targeted interventions might be beneficial. NCT02398799.