Introduction: The number of elderly patients undergoing hemodialysis is steadily increasing. The choice and management of vascular access (VA) in these patients are difficult, and the role of postoperative isometric exercises on native VA maturation in the elderly population is not clearly established. Objectives: To assess the effect of postoperative isometric exercises on native VA maturation in patients older than 75 years with advanced chronic kidney disease. Methodology: This was a randomized single-center study over a 24-month period. Postoperative isometric exercises were performed in the exercise group (EG), while the control group (CG) received usual care. Demographic data, muscle strength (using handgrip [HG] dynamometer), Doppler ultrasound (DUS), incidence of VA complications, and clinical and DUS maturation were assessed at 4 and 8 weeks. Results: A total of 27 patients were included (EG: 14, CG: 13). The mean age of the patients was 79.9 AE 2.8 years; 74.1% were men, and 59.2% had radiocephalic VA. Demographic data, HG, and DUS measurements were similar at baseline. DUS measurements significantly increased in both groups at the end of the study. A significant increase in HG (19.1 AE 7.8 kg vs. 22.9 AE 9.7 kg, P = 0.001) and the highest clinical (CG vs. EG: 46.2% vs. 78.6%; P = 0.049) and DUS maturation (CG vs. EG: 30.8% vs. 71.4%; P = 0.041) were observed in the EG at 8 weeks. Globally, medical or surgical VA complications were lower in the EG and mainly included significant stenosis (CG vs. EG: 23.1% vs. 7.1%), although no significant differences were observed. Conclusions: Once a native VA is indicated in elderly patients, postoperative isometric exercise should be considered in order to improve the odds of achieving a mature functional arteriovenous fistula. Further studies are required to support our findings in this population.