Spirituality is a multifaceted construct related to health outcomes that remains ill defined and difficult to measure. Spirituality in patients with advanced chronic illnesses, such as chronic heart failure, has received limited attention. We compared two widely used spirituality instruments, the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp) and the Ironson-Woods Spirituality/Religiousness Index (IW), to better understand what they measure in 60 outpatients with chronic heart failure. We examined how these instruments related to each other and to measures of depression and quality of life using correlations and principal component analyses. The FACIT-Sp measured aspects of spirituality related to feelings of peace and coping, whereas the IW measured beliefs, coping, and relational aspects of spirituality. Only the FACIT-Sp Meaning/Peace subscale consistently correlated with depression (r=-0.50, P<0.0001) and quality of life (r=0.41, P=0.001). Three items from the depression measure loaded onto the same factor as the FACIT-Sp Meaning/Peace subscale (r=0.43, -0.43, and 0.71), whereas the remaining 12 items formed a separate factor (Cronbach's alpha=0.82) when combined with the spirituality instruments in a principal component analysis. The results demonstrate several clinically useful constructs of spirituality in patients with heart failure and suggest that psychological and spiritual well-being, despite some overlap, remain distinct phenomena.