Heart failure (HF) is a debilitating disorder with a poor prognosis that affects nearly 6 million Americans. Major depression and inadequate self-care are common and interrelated behavioral problems in HF that diminish quality of life and increase the risks of hospitalization and death. Previous randomized controlled trials (RCTs) have shown that both of these problems are difficult to treat. Stepped care for major depression is a promising approach that has not been tested in patients with HF, and previous HF self-care trials have not addressed depression despite the fact that it has been found to be a significant barrier to self-care. The purpose of this randomized, single-blind, parallel groups, controlled clinical trial is to test a stepped care intervention for major depression in patients with HF and o determine whether HF self-care outcomes can be improved by treating depression before intervening in self-care. Outpatients with HF and comorbid major depression (n=180) will be randomly assigned to an 18-week stepped care intervention (SC) or to usual care (UC) for depression. The initial step in the SC intervention will be individual cognitive behavior therapy (CBT). The therapy will be augmented with an antidepressant medication at Week 6 if the early response to CBT is inadequate (<10% improvement in depression), and the antidepressant regimen will be modified at Week 12 if there has been <50% improvement by then. The antidepressant options will include sertraline, escitalopram, bupropion, and mirtazapine, and the choice will be guided by clinical evaluation. The CBT treatment plan will also be modified at Weeks 6 and 12 as needed, and will include a module for treatment of residual insomnia when indicated. The schedule of CBT sessions will be tapered if remission and relapse prevention criteria are met before 18 weeks. All participants in both arms will receive an individually tailored, nurse-directed HF self-care intervention between Weeks 18 and 24. Follow-up assessments will be conducted through Week 52 to evaluate maintenance of gains, and medical records will be obtained throughout the follow-up period to document hospitalizations and deaths. The outcomes will include remission of depression, improvement in HF self-care, and all-cause hospitalizations. Additional outcomes will include change in the severity of depression and anxiety, HF-related quality of life, fatigue, sleep quality, and social functioning.If this RCT demonstrates that stepped care is efficacious for major depression in patients with HF, and that treating depression before intervening in self-care improves self-care outcomes, it will help to establish this approach as an evidence- based clinical intervention for outpatients with heart failure. It will also help to pave the way for Phase III multicenter trial with a primary composite end point of hospitalization or death.