Medication adherence is important to heart failure (HF) self‐care. However, the rate of medication nonadherence is approximately 50%. Evidence suggests that self‐care activation and hope may be internal motivators for medication adherence. Empirical data on the association between self‐care activation, hope, and medication adherence among people with HF is sparse, and the mechanism by which these factors influence medication adherence is unclear. The findings of prior research studies suggest that resilience may help to explain the relationship between self‐care activation, hope, and medication adherence. The aim of this cross‐sectional study was to investigate whether resilience mediated the effects of self‐care activation and hope on medication adherence. A total of 174 adults with HF, between the ages of 19 and 92, completed the Patient Activation Measure, The Adult Hope Scale, the 14‐item Resilience Scale, and the Domains of Subject Extent of Nonadherence Scale. Mediation analyses revealed that resilience fully mediated the effects of self‐care activation and hope on medication adherence. Clinicians should consider the person related factors of self‐care activation, hope, and resilience when promoting medication adherence in people with HF. Resilience may play an important role in improving medication adherence in HF patients. More research is needed to understand the connection between resilience, self‐care activation, hope, and medication adherence.