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Introduction: Vascular access thrombosis increases the risk of mortality and morbidity in end-stage renal disease (ESRD) patients on hemodialysis (HD). This study aimed to evaluate hereditary thrombophilia factors in HD patients and its association with tunneled cuffed catheters’ thrombosis. Methods: In this cross-sectional study, 60 consecutive patients with ESRD on HD with tunneled cuffed catheters were selected. Inherited thrombophilia factors (Anti-thrombin III, Protein C, Protein S, and Factor V Leiden) were measured and the patients were followed for 3 months to evaluate the incidence of catheter-related thrombosis. The association between these factors and catheter thrombosis was assessed. Results: The mean age of patients was 60.30 ± 8.69 years. Forty-seven patients (78.30%) were female and thirteen patients (21.70%) were male. The most common cause of ESRD was diabetes mellitus (41.67%). The most catheter site was the right internal jugular vein (55%). There were 22 (36.67%) and 8 (13.33%) cases of thrombosis and mortality, respectively. The association between hereditary thrombophilia factors and catheter thrombosis was not statistically significant (P > 0.05). Conclusion: In this small group of our patients, the frequency of hereditary thrombophilia was not significantly different between those with and without thrombosis of tunneled HD catheter.