Abstract Background and Aims Ejection fraction (EF) and chronic heart failure (HF) are often considered as criteria for the possibility of arteriovenous fistula (AVF) creation in relation to an increased risk of death, without sufficient evidence for this. There is, however, rare but compelling evidence that low EF increases the risk of AVF dysfunction. Aims: to evaluate the association between EF at the time of AVF creation and the incidence of adverse cardiovascular events, all-cause mortality, as well as AVF dysfunction Method This retrospective cohort study included 962 adult patients who had a first-time created functioning AVF. Only patients with a more than three months period after AVF creation and within a five-year period were included. The mean follow-up period was 34 ± 13 months. Four groups were identified based on EF and the presence of HF at the time of AVF creation (transthoracic echocardiogram): HF with reduced EF (rEF) <40%, with mid-range (mrEF) of 40-49%, or with preserved EF (pEF) ≥50% + HF, and a “no HF” group with EF ≥50% and no HF. Results In the univariate analysis, a reduced EF was associated with an increased risk of mortality, with the hazard ratios (HRs) of 2.706 [95% CI 1.330; 5.507], p = 0.006 for mrEF and 8.250 [95% CI 2.621; 25.97], p < 0.001 for rEF, compared to the “no HF” group (here and thereafter)—Fig. 1. However, after adjusting for age, sex, and Charlson Comorbidity Index (CCI), the EF was not significantly associated with the risk of death. Only the CCI score remained a significant factor (HR = 1.748 [95% CI 1.482; 2.063], p < 0.001). A decreased EF was associated with the incidence of AVF dysfunction both in the univariate analysis and after adjustments. In the univariate analysis, the incidence rate ratios (IRRs) of 6.88 [95% CI 3.88; 12.1], p < 0.001 for mrEF, and 19.9 [95% CI 8. 64; 41.6], p < 0.001 for rEF, were shown. After adjusting for age, sex, and CCI, the IRR for mrEF was 8.96 [95% CI 5.81; 13.7], p < 0.001, and for rEF it was 23.4 [95% CI 13.8; 38.6], p < 0.001. Even in the presence of polycystic kidney disease and diabetes mellitus in the fully adjusted model, the association between EF and the incidence of AVF dysfunction remained statistically significant: the IRR was 8.61 [95% CI 5.61; 13.1], p < 0.001 for mrEF, and 33.4 [95% CI 19.5; 56.2], p < 0.001 for rEF. The findings were confirmed in a sensitivity analysis that included adjustments for unplanned onset of dialysis and competing risks survival analysis (death—outcome of interest, conversion of HD to PD or kidney transplantation and conversion of AVF to CVC—competing events). According to our results patients with EF<40% will inevitably lose AVF function for various reasons within 3.5 years—Fig. 2. Meanwhile, this approach will give the patient additional time of HD via AVF, but not CVC, without increasing the risk of death, subject to Qa monitoring. Conclusion In patients with CKD 5 who are initiating treatment with maintenance hemodialysis, a decreased EF is associated to a greater extent with a higher risk of AVF dysfunction than with an increased risk of mortality. The burden of comorbidities, rather than a standalone assessment of EF, is one of the major risk factors determining patient survival.