Purpose: Despite the growing evidence for effects of religious factors on cardiac health in general populations, findings are not always consistent in sicker and older populations. We previously demonstrated that short-term negative outcomes (depression and anxiety) among older adults following open heart surgery are partially alleviated when patients employ prayer as part of their coping strategy. The present study examines multifaceted effects of religious factors on long-term postoperative adjustment, extending our previous findings concerning prayer and coping with cardiac disease. Design and Methods: Analyses capitalized on a preoperative survey and medical variables from the Society of Thoracic Surgeons' National Database of patients undergoing open heart surgery. The current participants completed a mailed survey 30 months after surgery. Two hierarchical regressions were performed to evaluate the extent to which religious factors predicted depression and anxiety, after controlling for key demographics, medical indices, and mental health. Results: Predicting lower levels of depression at the follow-up were preoperative use of prayer for coping, optimism, and hope. Predicting lower levels of anxiety at the follow-up were subjective religiousness, marital status, and hope. Predicting poorer adjustment were reverence in religious contexts, preoperative mental health symptoms, and medical comorbidity. Including optimism and hope in the model did not eliminate effects of religious factors. Several other religious factors had no long-term influences. Implications: The influence of religious factors on the long-term postoperative adjustment is independent and complex, with mediating factors yet to be determined. Future research should investigate mechanisms underlying religion-health relations.