ABSTRACT Background Cardiorenal syndromes (CRS) are reputed to result in worse prognosis than isolated heart failure (HF) and chronic kidney disease (CKD). Whether it is true for all major outcomes over the long-term regardless of CRS chronology (simultaneous, cardiorenal and renocardiac CRS) is unknown. Methods The 5-year adjusted risk of major outcomes was assessed in this nationwide retrospective cohort study in all 385 687 with either CKD or HF (out of 5123 193 patients who were admitted in a French hospital in 2012). Results Overall, 84.0% patients had HF and 8.9% had CKD (they had similar age, sex ratio, diabetes and hypertension prevalence) while 7.1% had CRS (cardiorenal: 44.6%, renocardiac: 14.5%, simultaneous CRS: 40.8%). The incidence of major outcomes was 57.3%; 53.0%; 79.2% for death, 18.8%; 10.9%; 27.5% cardiovascular death, 52.6%; 34.7%; 64.3% for HF, 6.2%; 5.5%; 5.6% for myocardial infarction (MI), 6.1%; 5.8%; 5.3% for ischemic stroke, and 23.1%; 4.8%; 16.1% for end-stage kidney disease (ESKD) for isolated CKD, isolated HF and CRS, respectively. As compared to isolated CKD or HF, the risk of death, cardiovascular death and HF was markedly increased in CRS, the worse phenotype being cardiorenal CRS, while the increased risk of MI and ischemic stroke associated with CRS subtypes was statistically but not clinically significant. As compared to isolated CKD, the risk of ESKD was similar for cardiorenal syndrome only and marginally increased for renocardiac and simultaneous CRS. We could not find a synergy between HF and CKD on major clinical outcomes in the whole population (n = 5123 193 patients). Conclusions The additional impact of CRS vs isolated HF or CKD on long-term kidney and cardiovascular risk is highly heterogenous, depending of the event considered and CRS chronology. No synergy between HF and CKD could be demonstrated.