OBJECTIVE: To determine the effect of losartan on aortic dilatation rate in adults with Marfan syndrome. DESIGN: Randomised, controlled multicentre clinical trial. METHOD: Adult Marfan patients from the 4 Marfan centres in the Netherlands with a maximum of 1 aortic prosthesis were randomised to 100 mg losartan once daily or no additional losartan treatment. All patients continued their standard treatment, which consisted mainly of beta-blockers. The primary outcome measure was a reduction in aortic dilatation rate. The secondary outcome measures were an increase in aortic volume and the incidence of the combined outcome measure: cardiovascular mortality, aortic dissection and aorta surgery. This trial was registered with the Dutch Trial Register (NTR1423). RESULTS: 233 patients were included. Absolute aortic diameters were measured at the beginning and at the end of the study. The aortic root dilatation rate after 3 years was significantly lower in patients in the losartan group than in those in the control group (0.77 mm/3 years (SD: 1.36) vs. 1.35 mm/3 years (SD: 1.55); p = 0.014). The dilatation rate in the trajectory beyond the aortic root was comparable in the two groups. There were no differences in the secondary outcome measures between the two groups. A subanalysis of patients with aortic root replacement surgery prior to inclusion in the study demonstrated that in this group losartan treatment led to a significant decrease in aortic arch dilatation rate versus standard treatment (0.50 mm/3 years (SD: 1.26) vs. 1.01 mm/3 years (1.31); p = 0.033). CONCLUSION: In adult Marfan patients, losartan treatment reduces the aortic root dilatation rate. After aortic root surgery, losartan treatment reduces dilatation rate of the aortic arch.