Introduction: Vegan diets, where animal- and all their by-products are excluded from the diet, have gained popularity. Growing evidence suggests potential cardiovascular benefits of vegan diets due to improvements in diet quality (i.e., higher consumption of vegetables, fruits whole grains, nuts, legumes, and seeds). Methods: The TwiNS randomized controlled trial examined the cardiometabolic impact of a healthy vegan diet compared to a healthy omnivorous diet (NCT05297825). These diets were examined in 22 pairs of identical twins, where one twin followed the vegan diet, and the other twin followed the omnivorous diet for 8 weeks. Diet specific meals were provided via a meal delivery service from baseline through week 4, and during weeks 5-8 participants prepared their own diet appropriate meals and snacks. The primary outcome was difference in LDL cholesterol from baseline to week 8. Secondary outcome measures included change in triglycerides, HDL-cholesterol and body weight. Adherence to study diets, ease/difficulty in following the diets, participant energy levels, and sense of wellbeing were also measured. A linear mixed model was used to investigate a difference in the change in primary and secondary outcomes from baseline and included a random effect for twin pair, to account for the correlation between identical twins. Results: Participants were generally healthy adults, average age 39.6 years, primarily non-Hispanic White, and had an average BMI of 26.2. On average, twins randomized to the healthy vegan diet had decreased their LDL-cholesterol more after 8 weeks compared to twins on the healthy omnivorous diet (-15.2 vs. -2.3mg/dL, 95% CI: 4.3-24.8). Participants on the healthy vegan diet also had decreased their body weight more after 8 weeks (-1.9 vs. -0.29 kg, 95% CI: 0.9-3.0). No significant differences were observed between the vegan and omnivorous diets for secondary outcomes of triglycerides or HDL-C. Conclusion: This study contributes to growing evidence that vegan diets may offer a protective cardiometabolic advantage compared to a healthy, omnivorous diet. Further analyses of the TwINS trial will examine changes to the gut microbiome (i.e., microbial diversity), inflammatory markers, and other health factors.