The multicentre, open-label COMPARE (COzaar in Marfan Patients Reduces aortic Enlargement) trial showed a small but significant beneficial effect of 3-year losartan treatment on aortic root dilatation rate in adults with Marfan syndrome (MFS). In this multicentre, open label trial 233 patients were randomized to either losartan on top of regular treatment, or to regular treatment. However, no significant effect was found on clinical endpoints, possibly due to a short follow-up period. The current study now investigates the long-term clinical outcomes in 153 of these patients after losartan treatment with a median follow-up period of 8 years. The clinical endpoints, defined as all-cause mortality, aortic dissection/rupture, elective aortic root replacement, reoperation, and vascular graft implantation beyond the aortic root, were compared between the two groups. Patients who used losartan during the entire follow-up period showed a reduced number of events compared to the control group (death: 0 vs. 5, P = 0.014; aortic dissection: 3 vs. 11, P = 0.013; elective aortic root replacement: 10 vs. 13, P = 0.264; reoperation: 1 vs. 2, P = 0.463; vascular graft implantations beyond the aortic root 0 vs. 3, P = 0.071; and composite endpoint: 14 vs. 26, P = 0.019). These results suggest a clinical benefit of combined losartan and β-blocker treatment in patients with MFS.