Objective: To observe the effects of blood purification treatment and assess the prognostic impact of different vascular pathways on patients with chronic renal failure (CRF). Methods: A retrospective analysis of clinical data was conducted on 68 CRF cases, categorizing them based on their choice of blood purification vascular access. Group A received an autologous arteriovenous fistula, Group B received an internal jugular vein tunneled polyester sleeve catheter, and Group C received a polytetrafluoroethylene graft vascular fistula. Clinically relevant observation indicators, complication rates, and quality of life scores among the three groups were compared. Results: No significant differences were found between the three groups regarding observed values of clinically relevant indicators and quality of life scores (P > 0.05). When comparing thromboembolism rates Group A had the highest rate, followed by Group C and Group B; for infection rate comparison, Group C had the highest rate, followed by Group B and Group A (P < 0.05). Conclusion: In comparison with the other two vascular access methods, although autologous arteriovenous fistula poses a higher risk of thromboembolism, it exhibits a lower infection rate. Therefore, it is recommended as the preferred vascular access form for blood purification in patients with CRF. If this approach is unavailable, careful consideration should be given. The use of an internal jugular vein with a tunneled polyester sleeve catheter is suggested to better ensure the effectiveness and safety of the patient’s treatment.