Subclavian vein thrombosis is a well-recognized complication following central venous catheter insertion and is associated with significant morbidity. The factor V Leiden mutation is an important risk factor for deep venous thrombosis and pulmonary embolism. Whether this mutation also predisposes patients fitted with a central venous catheter to subclavian vein thrombosis is not known. The occurrence of central venous catheter-associated thrombosis was investigated in 277 consecutive patients receiving an allogeneic bone marrow transplantation. All patients received a tunnelled double or triple catheter positioned in the subclavian vein. Catheter-associated thrombosis was diagnosed on the basis of clinical signs of thrombosis, i.e. swelling and/or redness of the limb or venous engorgement and was confirmed with a colour-flow Doppler ultrasound. Thirteen patients were heterozygous for the factor V Leiden mutation. Seven of these patients had a subclavian vein thrombosis (54%), while this occurred in only 9% of the factor V Leiden-negative patients, corresponding with a relative risk of 7.7 (95% CI 3.3-17.9). Factor V Leiden is attributable for 17.3% of all thrombosis in patients with central venous catheters. The majority of patients with the factor V Leiden mutation with a central venous catheter will develop thrombosis. Patients with a factor V Leiden mutation should receive adequate thrombosis prophylaxis upon catheter introduction and the catheter should be removed immediately after the treatment. Based on this very high risk, we advise testing for factor V Leiden in all bone marrow transplantation patients receiving a central venous catheter.