<p>The study was conducted to determine the spiritual well-being levels of heart failure (HF) patients and to evaluate the relationship between spiritual well-being, symptom control, and medication adherence. A total of 224 HF patients treated in a hospital in Türkiye were included in this descriptive and correlational study. Data were collected using a patient information form, Spiritual Well-Being Scale, Adherence to Refills and Medications Scale (ARMS-7), and Symptom Status Questionnaire-Heart Failure. The mean score of HF patients on the Spiritual Well-being Scale was 127.74 ± 4.54. Considering that the score range of the Spiritual Well-Being Scale is 29–145, it was determined that the scale score of the patients was high. The mean score of the ARMS-7 was 26.27 ± 1.41, and the mean score of the Symptom Status Questionnaire-Heart Failure was 33.12 ± 11.96. A high level of spiritual well-being was associated with decreased the impact of disease-related symptoms and increase medication adherence in HF patients (<i>p</i> &lt; 0.05). Additionally, regression analysis revealed that transcendence was associated with symptom burden (adjusted R² = 0.046) and medication adherence (adjusted R² = 0.062) (<i>p</i> &lt; 0.01). As a result of our study, spiritual well-being was found to be associated with medication adherence and symptom control, although at a low level. Within the framework of holistic care, it is essential to strengthen the spiritual well-being levels of HF patients to support disease management. Longitudinal studies with larger sample sizes may be recommended to examine the relationship between spiritual well-being, medication adherence, and symptom control variables in HF patients.</p>