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Introduction The role of losartan in preventing aortic root dilatation in Marfan syndrome has been evaluated in many clinical trials; however, the results are conflicting. Methods We performed a computerized search of MEDLINE, EMBASE and COCHRANE databases through February 2019 for randomized clinical trials evaluating the effect of losartan in patients with Marfan syndrome. The main outcome was the change in the aortic root diameter in the losartan versus control groups. Results Our final analysis included seven randomized trials with a total of 1352 patients and average weighted follow-up of 37.8 months. Change in aortic root diameter was significantly smaller with losartan compared with control [weighted means: 0.44 vs. 0.58 mm, mean difference (MD) = −0.13; 95% CI −0.24 to −0.02; p = 0.02]. Subgroup analysis according to the control group showed no significant subgroup interaction when comparing losartan with beta-blockers versus with standard therapy (pinteraction= 0.27). The composite outcome of aortic surgery, dissection or mortality did not differ between the losartan and control groups (risk ratio = 1.03; 95% CI 0.72–1.49, p = 0.86). Conclusion In this meta-analysis including seven randomized trials, the use of losartan was associated with a significantly smaller change in aortic root diameter in patients with Marfan syndrome. Electronic supplementary material The online version of this article (10.1007/s40119-019-00149-3) contains supplementary material, which is available to authorized users.