Objectives: Vascular Ehlers-Danlos Syndrome (VEDS) is a rare connective tissue disorder impacting type III collagen production. We aim to delineate the impact of sex on variation in aortopathy, arteriopathy, and mortality among patients with VEDS. Methods: A cross-sectional analysis of 557 patients with VEDS and COL3A1 pathogenic variants was performed. Primary outcomes were distribution of aortopathy and arteriopathy, and all-cause mortality. Statistical analysis was performed utilizing Student’s t-tests (continuous data) and Pearson’s c2 tests (categorical data). Results:  In the cohort, males were younger (35.8±16.6 vs. 39.2±16.0 years, P=0.017) and had more diagnoses of hypertension (16.1% vs. 8.1%, P=0.003), inguinal hernias (10.9% vs. 0.6%, P<0.001), and spontaneous pneumothoraces (10.5% vs 5.8%, P=0.043) compared to females. There was no difference in age of VEDS diagnosis, family history, or genotype frequency between males and females. Additionally, there were no statistical differences in stroke, myocardial infarction, intestinal perforation, musculoskeletal conditions. Aortopathy and arteriopathy differed between sexes. Aortopathy and arteriopathy was more common in males (74.2% vs. 57.9%, P<0.001), with more involvement of the visceral arteries (29% vs 18.4%, P=0.003), iliac arteries (23.8% vs 14.9%, P=0.008), and aorta (35.5% vs. 18.8%, P<0.001). Females had more frequent carotid cavernous fistulae (CCF, 6.2% vs 0.8%, P<0.001), carotid and great vessel involvement (23.6% vs. 15.7%, P = 0.21), and spontaneous coronary arterial dissection (SCAD, 3.2% vs 0.8%, P=0.05). Males had higher all-cause mortality (32.3% vs 20.4%, P=.001). Conclusions:  Males with VEDS had more visceral artery, iliac artery, and aortic involvement, and females had greater frequency of SCAD, CCF, and carotid and great vessel involvement. These findings are similar to aortic and arterial disease in the general population. Unlike the general population, the age of onset appears to be similar between males and females with VEDS. These findings demonstrate sex-based differences in VEDS manifestation and highlight potential gaps in our understanding of patient risk factors.