Abstract Background and Aims The demographic characteristics of incident and prevalent hemodialysis (HD) patients have been undergoing significant changes over the last decades, in what has been called an “epidemic of aging in renal replacement therapy” 1. The higher proportion of very elderly patients has brought significant challenges to the nephrologists, namely regarding the choice and timing of vascular access (VA) creation. Despite the arteriovenous fistula (AVF) undeniable status has the preferred VA, the applicability of the “Fistula First” initiative in very elderly patients has been questioned. Method This single-center observational retrospective cohort study took place at the Coimbra Hospital and University Centre, a Portuguese tertiary referral hospital. Patients were selected from the Nephrology department's database of HD referrals. Inclusion criteria were HD referral between January 2017 and December 2021 and age equal or over 80-years old at time of referral. We collected data regarding demographic characteristics, comorbid conditions, first VA, pre-HD nephrology care and functional status at referral, as well as the time and cause of death during the follow-up period. Functional status was assessed through the Katz index of independence in activities of daily living and the comorbid conditions were assessed through the Charlson comorbidity index. Primary outcome was mortality, and follow-up ended on the 31st of May 2022. Variables associated independently with mortality were included in Cox proportional-hazards regression models. Results Our study sample included 288 patients, predominantly male (63.9%), with a median age of 83 and a diabetes prevalence of 42.8%. The VA at first dialysis was a central venous catheter (CVC) in 77.8% and 68.1% had an unplanned HD start. Eighty-four percent had at least 3 months of pre-HD nephrology care. The mean Charlson Index at HD referral was 9.1 and 50.6% presented a Katz index under 5. The mortality incidence rate during follow-up was 32.8/100 patient-year, with 90-days, one-year, and two-year survival rates of 88.2%, 69.1% and 51.4%, respectively. The main known causes of death were infections not related with the VA (29%) and cardiovascular disease (14%). Starting HD through a CVC was associated with worse survival in univariate analysis (Log-rank 15.4, p<0.001). Other mortality-related variables in survival analysis were age at HD referral hazard ratio (HR) 1.082, p<0.001, absence of pre-HD nephrology care (Log-rank 14.6, p<0.001), urgent-start HD (Log-rank 24.3, p<0.001), Katz index (HR 0.67, p<0.001) and Charlson index (HR 1.28, p<0.001). In a Cox Proportional Hazards model, when adjusting for the other mortality predictors, CVC use at first HD and unplanned HD start did not present a statistically significant association with mortality (HR 1.587, p = 0.074; HR 1.508, p = 0.098, respectively). Conclusion In our study sample, most patients started HD through a CVC, despite the majority having at least 3 months of pre-HD nephrology care. When adjusting for other covariates in a multivariate model, the first VA did not present a strong association with survival outcomes. The appropriate VA in the very elderly patient is an ongoing debate, and doubts remain regarding the applicability of the “Fistula First, Catheter Last” policy in octogenarian and nonagenarian patients. Our results are in line with recent reports which suggest that initial CVC use with later placement of an AVF, shortly after HD initiation, does not confer worse prognosis than initial AVF use in very elderly patients 2. One of the limitations of our study was not having collected data regarding timings of AVF construction and use, which might have been informative regarding the impact of catheter-dependence time in survival.