Aims: Patient-reported outcome measures (PROMs) may predict poor clinical outcome in patients with heart failure (HF). It remains unclear whether PROMs are associated with subsequent adherence to HF medication. We aimed to determine whether health-related quality of life, anxiety, and depression were associated with long-term medication adherence in these patients. Methods and results: A national cohort study of Danish patients with HF with 3-year follow-up (n = 1464). PROMs included the EuroQol five-dimensional, five-level questionnaire (EQ-5D-5L), the HeartQoL and the Hospital Anxiety and Depression Scale (HADS). Patient-reported outcomes (PRO) data were linked to demographic and clinical data at baseline, and data on all redeemed prescriptions for angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers/angiotensin receptor neprilysin inhibitors (ACEI/ARB/ARNI), β-blockers, and mineralocorticoid receptor antagonists during follow-up. Medication non-adherence was defined as <80% of proportion of days covered. In adjusted regression analyses, lower health-related quality of life (EQ-5D and HeartQoL) and symptoms of depression (HADS-D) at discharge were associated with non-adherence. After 3 years of follow-up, lower health-related quality of life (EQ-5D) was associated with non-adherence for ACEI/ARB/ARNI [adjusted OR 2.78, 95% confidence interval (CI): 1.19-6.49], β-blockers (adjusted OR 2.35, 95% CI: 1.04-5.29), whereas HADS-D was associated with non-adherence for ACEI/ARB/ARNI (adjusted OR 1.07, 95% CI: 1.03-1.11) and β-blockers (adjusted OR 1.06, 95% CI: 1.02-1.10). Conclusion: Lower health-related quality of life and symptoms of depression were associated with non-adherence across HF medications at 1 and 3 years of follow-up. Person-centred care using PROMs may carry a potential for identifying patients at increased risk of future medication non-adherence.