Vascular access thrombosis represents a serious and unfortunately common problem in hemodialysis patients. Usually, but not always, this complication can be attributed to low access blood flow. However, there are some patients who experience thrombosis despite a well functioning vascular access. We describe the case of a 31-year-old Caucasian male, who was hemodialyzed via an arteriovenous fistula for two years due to Alport's syndrome. During this time period he had two episodes of vascular access thrombosis that destroyed two arteriovenous fistulas. Both fistulas were functioning well and the thrombosis events took place in days between the hemodialysis sessions. Thrombophilia was suspected and the relative investigation revealed high levels of factor VIII procoagulant, which is frequent in hemodialysis patients, and resistance to activated protein C. Polymerase chain reaction detected that the patient was heterozygous for factor V Leiden, which is quite common in general population. Thereafter, a new arteriovenous fistula was formed and the patient started oral anticoagulation therapy with warfarin. Now, three years after the last arteriovenous fistula formation, the patient is hemodialyzed without vascular access problems. In conclusion, evaluation of the coagulation cascade in hemodialysis patients with recurrent vascular access thrombosis is necessary.