Patients with congestive heart failure (CHF) often report high levels of religiousness, which may mitigate the stressfulness of their condition. However, religious struggle, reflecting negative attitudes toward God and a strained meaning system, may be detrimental to wellbeing. Little is known about religious struggle in those with CHF, particularly in relation to physical health and wellbeing over time. We examined associations of religious struggle and subsequent mental and physical well-being in 101 endstage CHF patients who completed questionnaires twice over 3 months. Religious struggle predicted higher number of nights subsequently hospitalized, higher depression, and marginally lower life satisfaction. When controlling for baseline levels of well-being, effectively assessing change in those outcomes, religious struggle remained a significant predictor of hospitalization and also emerged as a marginally significant predictor of lower physical functioning. Struggle was unrelated to health-related quality of life. Post-hoc analyses suggest that these effects were particularly strong for those endorsing greater religious identification. Religious struggle appears to have a potentially negative impact on well-being in advanced CHF; therefore, helping patients to address issues of struggle may meaningfully lessen the personal and societal costs of CHF.