BACKGROUND/AIMS: Infection remains the second leading cause of mortality in patients with end-stage renal disease (ESRD). Despite the direct relationship between hemodialysis vascular access-related infections (HD-VARI) and both prognosis and mortality in ESRD patients, there is a paucity of research in this area. METHODS: This retrospective study was performed at a tertiary care hospital in Seoul, Korea, from 2009 to 2020. Medical records of adult patients diagnosed with HD-VARI were assessed. We analyzed the distribution of microorganisms, clinical characteristics according to vascular access type, and evaluated risk factors for treatment failure. RESULTS: Data from a total of 367 patients were included over the 12-year study period. Based on vascular access type, 293 (79.8%) had arteriovenous graft infections, 29 (7.9%) had arteriovenous fistula infections, and 45 (12.3%) had tunneled cuffed catheter infections. Thirty-one (8.4%) patients experienced treatment failure within 90 days. Multivariate analysis identified male sex (odds ratio [OR], 2.343; 95% confidence interval [CI], 1.041-5.274) and metastatic infection (OR, 4.297; 95% CI, 1.516-12.178) as independent predictors of 90-day infection-related treatment failure. Subtotal or total excision (removal) of the infected vascular access significantly decreased the risk of 90-day infection-related treatment failure (OR, 0.337; 95% CI, 0.129-0.876). CONCLUSION: Removal of infected vascular access played a crucial role in reducing infection-related deaths or relapses within 90 days. Management of vascular access infection should be individualized based on patient-specific factors.