Depression increases the risk of mortality in patients with heart failure (HF). Less is known about whether depression predicts multiple readmissions or whether multiple hospitalizations worsen depression in patients with HF. This study aimed to test the hypotheses that depression predicts multiple readmissions in patients hospitalized with HF, and conversely that multiple readmissions predict persistent or worsening depression. All-cause readmissions were ascertained over a 2-year follow-up of a cohort of 400 patients hospitalized with HF. The Patient Health Questionnaire-9 was used to assess depression at index and 3-month intervals. At enrollment in the study, 21% of the patients were mildly depressed and 22% were severely depressed.