The aim of this study was to disclose the differences of surgical outcomes between Marfan syndrome with mutations in fibrillin-1 gene and Loeys-Dietz syndrome with mutations in transforming growth factor-beta receptor 1 and 2. We reviewed 368 patients aged less than 50years who underwent surgery for thoracic aortic diseases between 1988 and 2019, and enrolled 99 patients with Marfan syndrome (26.9%; 57 men, 33±7.5years) and 24 patients with Loeys-Dietz syndrome (6.5%; 13 men, 28±11years). Freedom from all causes of mortality was similar between the 2 groups (P=.40, log-rank). The cumulative incidence of reintervention was significantly lower in the Marfan syndrome group than in the Loeys-Dietz syndrome group (P=.016, Gray). The cumulative incidence of first aortic arch reoperation for aortic arch aneurysm was significantly lower in the Marfan syndrome group than in the Loeys-Dietz syndrome group (P<.001, Gray). The cumulative incidence of first aortic root reoperation for aortic root aneurysm (P=.57, Gray) and first descending aorta reoperation for descending aortic aneurysm (P=.76, Gray) was similar between the 2 groups. The cumulative incidence of aortic dissection after initial surgery was significantly lower in Marfan syndrome than in Loeys-Dietz syndrome (P=.0059, Gray). Loeys-Dietz syndrome with mutations in transforming growth factor-beta receptor 1 and 2 revealed higher rates of reoperation, and more specifically the arch reoperation was higher in those with Loeys-Dietz syndrome than those with Marfan syndrome. Aggressive arch surgery in the initial operation on the proximal aorta is recommendable in Loeys-Dietz syndrome to avoid additional aortic events. In Marfan syndrome, this is controversial in patients without dissection because of a low possibility to expand.