BACKGROUND: Venous thromboembolism (VTE) following breast cancer chemotherapy is common. Chemotherapy-induced alterations in markers of haemostasis occur during chemotherapy. In this study we investigated the changes in serum and plasma VEGF, together with platelet release of VEGF and related these to the development of VTE at 3 months. METHODS: Serum and plasma VEGF, together with platelet release of VEGF were measured prior to chemotherapy and at 24 hours; four-, eight days and three months following commencement of chemotherapy in early and advanced breast cancer patients and in age and sex matched controls. Duplex ultrasound imaging was performed after one month or if symptomatic. RESULTS: Of 123 patients 9.8% developed VTE within three months. Serum and plasma VEGF were increased in advanced breast cancer as was platelet release of VEGF. Prior to chemotherapy a 100 mug/ml increase in serum VEGF was associated with a 40% increased risk of VTE, while a 10 mug/ml increase in plasma VEGF was associated with a 20% increased risk of VTE. Serum VEGF showed a different response to chemotherapy in those who developed VTE. CONCLUSION: A group of patients at risk of VTE could be identified, allowing targeted thrombopropylaxis. Whether or not the response in VEGF during chemotherapy has any angiogenic significance remains to be elucidated.