Indoxyl sulfate (IS), a uremic toxin, is associated with mortality and cardiovascular events in patients with chronic kidney disease (CKD). This study aimed to evaluate the prognostic implications of serum IS levels in patients with heart failure and CKD. This was a prospective multicentre observational study. Overall, 300 patients with chronic heart failure with a previous history of hospitalisation and an estimated glomerular filtration rate of 45 mL/min/1.73 m2 or less without dialysis were analysed. The primary outcome assessed was a composite of all-cause death, hospitalisation for heart failure, nonfatal myocardial infarction, and nonfatal stroke. Clinical events were followed up to one year the measurement of IS. The median patient age was 75 years, and 57% of the patients were male. We divided the cohort into low and high IS categories according to a median value of 9.63 mg/mL. The primary outcome occurred in 27 of 150 patients in the low IS group and 27 of 150 patients in the high IS group (hazard ratio, 1.00; 95% confidence interval, 0.58 to 1.70). The results were consistent across various subgroups. Among heart failure patients with CKD, serum IS concentrations were not significantly associated with the subsequent occurrence of cardiovascular events.