The majority of vascular access thrombosis episodes in hemodialysis patients are due to anatomic abnormalities. Thrombophilias are inherited, acquired or mixed disorders which also predispose to venous thromboembolism. They include protein C, protein S and antithrombin deficiencies, as well as gene mutations for prothrombin and factor V Leiden. The most important of the mixed cases is hyperhomocysteinemia, which includes both a genetic and an acquired substrate. We report two patients undergoing hemodialysis who suffered from multiple thrombotic events, the first due to factor V Leiden heterozygosity and the second because of hyperhomocysteinemia due to homozygosity for MTHFR C677T mutation. As no site for vascular access was left, transfer to peritoneal dialysis for both patients improved solute clearance and quality of life with no additional thrombotic events noted.