Background: Heart failure (HF) is a disabling chronic illness that is increasing in prevalence. Despite advances in its medical treatment, little is known about its psychosocial correlates. This investigation compared the prevalence of depression in patients with and without HF who were hospitalized with myocardial infarction (MI) and also at high psychosocial risk. Methods: Baseline data from the 2444 participants in the ENRICHD clinical trial were used. Within 28 days of the MI, all patients were assessed for depression using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria, for HF based upon left ventricular dysfunction or history of HF and for demographic and medical confounders. Results: Eight hundred forty-seven patients (34.7%) met the criteria for HF. Major depression was observed in 43% in the HF group compared with 36% in the non-HF group (P < .001). Multivariate modeling showed a 38% increase in odds of HF for patients with major depression, after adjustment for sociodemographic factors and medical comorbidities (adjusted OR 1.38, 95% CI 1.09-1.76). Conclusions: These findings suggest that in patients with new MI who are at psychosocial risk, major depression is more prevalent in those who also have HF. Because major depression undermines adherence and lowers quality of life, special efforts to diagnose and treat it in post-MI patients with HF appear warranted. © 2005, Mosby, Inc. All rights reserved.