Abstract Context Large extracellular vesicles (lEVs) enriched for endothelial and blood cell markers are increased in metabolic conditions such as obesity or type 2 diabetes (T2D), actively contribute to the atherosclerotic process, and have been identified as diagnostic and prognostic biomarkers for cardiovascular disease (CVD). Although bariatric surgery (BS) in individuals with obesity is related to decreased cardiovascular (CV) risk and increased life expectancy, after BS these subjects are still at higher CV risk than the general population. Objective We aimed to compare the lEV profiles between individuals with obesity, with or without T2D, before and 1 year after BS, and normal-weight controls. Methods Prospective longitudinal study with individuals eligible for BS, with or without T2D (T2D and OB groups, respectively) and healthy controls (HC group) matched by age and sex. The concentration and phenotype of lEVs were assessed by flow cytometry. Results The study cohort included 108 individuals (age 48.0 ± 10.5 years; 84.3% females). Before BS, the OB group presented higher concentrations of lEV enriched for endothelial and blood cell biomarkers than the HC group, but lower concentrations than those observed in the T2D group (P < .05). BS resulted in a significant reduction in most of the lEVs enriched for cell-specific markers in both subgroups. lEV differences between OB and T2D groups were no longer observed after BS (P > .05). However, compared with HC group, OB and T2D groups still showed increased concentrations of lEVs enriched for platelet and endothelial cell markers (P < .05). Conclusion At 1 year after BS, lEV concentrations remain above the physiological range. These abnormalities might contribute to explaining the increased CV risk after BS and underscore the importance of long-term CV risk factor control in post-BS individuals.