Background <p>Hemodialysis is the most prevalent modality of renal replacement therapy. The durability of hemodialysis and its quality depend on consistent and reliable access to the patient’s vascular system. In this systematic review we provide a comprehensive analysis of the predictors of primary arteriovenous fistula failure.</p> Methods <p>A systematic search was conducted in PubMed, Web of Science, ScienceDirect, and the WHO Virtual Health Library Regional Portal from database inception through March 2025. Search terms included combinations of ‘arteriovenous fistula’, ‘failure’, ‘hemodialysis’, ‘end-stage renal disease’, and ‘risk factors’. Four reviewers independently screened titles and abstracts, with full texts assessed according to predefined inclusion criteria. Studies were eligible if they examined risk factors for primary arteriovenous fistula failure in adult patients on hemodialysis.</p> Results <p>A total of 38 studies were included in the systematic review. Early arteriovenous fistula failure was significantly associated with a distal location of the fistula, small arterial diameter, small vein diameter, low serum albumin level, female gender, diabetes mellitus, and decreased systolic and diastolic blood pressure.</p> Conclusion <p>This systematic review identified several key risk factors for early arteriovenous fistula failure in patients with end-stage renal disease (ESRD) undergoing hemodialysis. These factors should be considered from a patient safety perspective and included in the shared decision-making process with patients who are candidates for arteriovenous fistula surgery. Optimizing these factors may enhance fistula maturation and reduce the need for repeat vascular access procedures. However, recognizing that some risk factors may not be readily modifiable in ESRD patients, clinicians should balance optimization efforts with the urgency of establishing vascular access.</p>