This double blind randomized controlled trial was designed to investigate whether short-term vitamin E treatment at doses of 500 and 1000 mg/day, compared to placebo, decreased urinary F(2)-isoprostanes and improved the microvascular perfusion after cold exposure in patients suffering from SSc. Thirty-three eligible patients were randomly assigned in a 1.3:1:1 ratio to receive placebo, vitamin E 500 mg, or vitamin E 1000 mg daily for 3 weeks. Clinical examination, analysis of plasma vitamin E, urinary F(2)-isoprostane levels and a whole body cooling test were performed at baseline and after a 3-week period of treatment. Urinary 15-F(2t)-IsoP levels and cutaneous blood flow variation in response to cold did not significantly differ before versus after treatment in any group. Furthermore, no difference was found between groups after 3 weeks of treatment. We show that 3-week vitamin E treatment at doses of 500 or 1000 mg/day neither decreases the basal rate of lipid peroxidation nor improves microvascular perfusion after cold exposure. These data does not support the need for phase III clinical trials to test efficacy of vitamin E in SSc.