OBJECTIVE: This study examined whether the severity of left ventricular systolic dysfunction is associated with depression in patients with heart failure (HF). Other factors were also studied to identify independent correlates of depression in HF. METHODS: The sample consisted of 400 hospitalized patients with HF. Left ventricular ejection fraction and other medical data were obtained from medical records. Depression and other psychosocial characteristics were assessed by an interview and questionnaires. Proportional odds models were used to test the relationships of these characteristics to Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) depressive disorders, and analysis of covariance was used to test relationships with continuous measures of depression in secondary models. RESULTS: The models produced no evidence of an association between left ventricular ejection fraction and depression. The adjusted odds ratio (95% confidence interval) was 1.00 (0.98-1.01; p = .87) for depression diagnosis. Analysis of covariance estimates (standard errors) were -0.01 (0.02; p = .54) for the Hamilton Rating Scale for Depression and -0.01 (0.01; p = .59) for the Patient Health Questionnaire. The odds of depression were higher in African American patients and in those with high levels of anxiety or stress. Other characteristics that have been associated with depression in previous studies, including sex and age, were not consistently associated with depression in this study. CONCLUSIONS: There is no relationship between the severity of left ventricular systolic dysfunction and depression in hospitalized patients with HF. In contrast, African American patients and those with a high level of anxiety or perceived stress are more likely than other patients to have a comorbid depressive disorder.