Background: Although spouses are a key support for patients with heart failure, and help them remain in the community, no one has studied patient-spouse pairs to determine the nature of their experience. Therefore, we conducted a study of patients and spouses to compare their levels of depression and health-related quality of life (HRQOL), and to identify factors that contribute to depression and HRQOL in patient-spouse pairs. Methods: Forty-eight couples, in which all patients were men with heart failure, were recruited from a university-affiliated, outpatient heart failure clinic. Data were collected using the Beck Depression Inventory, the 12-item Short Form (that measures physical and mental components of QOL), and the 6-minute walk test. Results: Patients with heart failure were significantly more depressed and had poorer physical quality of life compared with spouses. Patients' depression was correlated with their own functional status and mental quality of life, with the combination of 6-minute walk distance and mental QOL contributing 51% of the variance in patient depression. Spouse depression and HRQOL did not significantly influence patient depression. In contrast, spouses' depression was related to their husbands' functional status and employment, as well as their own mental QOL. The mental component of spouse QOL and the age of the patient accounted for 33% of the adjusted variance in spousal depression. Conclusions: Patients with heart failure and their spouses experience significantly different levels of depression and physical QOL. In developing interventions, it may be important to take these differences into account and focus on their unique needs as well as those issues that affect the couple together. Interventions that improve patient functional status may result in decreased depression and improved HRQOL on the part of both patients and spouses.