The number of patients with heart failure is increasing with aging population in Japan. Cardio-renal interaction plays an important role in the pathophysiology of heart failure. Recent studies showed that chronic kidney disease (CKD) is associate with an increased risk of cardiovascular events. However, mechanisms underlying between CKD and cardiovascular events remains unclear. In this study, indoxyl sulfate, an uremic toxin, was measured in patients with heart failure and its association with prognosis was evaluated in a multicenter cohort. Indoxyl sulfate levels in patients with heart failure were significantly associated with the incidence of cardiovascular events including cardiovascular death, stroke, acute myocardial infarction in patients with heart failure. These results suggest that indoxyl sulfate could be a therapeutic target in patients with heart failure and CKD.