AIMS: This study was designed to assess whether the prognostic significance of estimated glomerular filtration rate (eGFR) and left ventricular ejection fraction (LVEF) interact in populations with heart failure (HF) and myocardial infarction (MI). METHODS: Patients were recruited from four screening registers (N=18,010) including patients admitted with HF or MI. Ten years follow-up was recorded and formal testing for interactions between eGFR and LVEF with respect to outcome was done. RESULTS: Twelve-thousand-and-ninety patients died. A significant interaction (P=0.010) was found and each parameter became relatively more important when the value of the other was low. eGFR and LVEF were reparameterized to categorical variables and we observed that chronic kidney disease stage II was associated with a decreased (Hazard ratio (HR): 0.79 (95% Confidence Interval: 0.72-0.86)) and chronic kidney disease stages IV (HR: 1.60 (1.45-1.91) and V (HR: 1.91 (1.45-2.52) were associated with an increased mortality risk with an additive effect of left ventricular systolic dysfunction (LVSD). CONCLUSION: The prognostic significance of eGFR and LVEF is synergistic in patients with HF or MI and the impact of one parameter is inversely related to the level of the other. Statistical interactions are scale dependent and the relationship between chronic kidney disease stages I to V and mortality risk is J-shaped with an additive effect of LVSD.