Markers of early pancreatic islet graft dysfunction and its causes are lacking. We monitored 19 T1D islet-transplanted patients for up to 36 months following last islet injection. Patients were categorized as Partial (PS) or complete (S) Success, or Graft Failure (F), using the β-score as an indicator of graft function. F was the subset reference of maximum worsened graft outcome. To identify the immune, pancreatic, and liver contribution to the graft dysfunction, the cell origin and concentration of circulating micro vesicles (MVs) were assessed, including MVs from insulin-secreting ß-cells typified by PSA-NCAM, and data were compared with values of the β-score. Similar ranges of PSA-NCAM+ -MVs were found in healthy volunteers and S patients, indicating minimal cell damage. In PS, a 2-fold elevation in PSA-NCAM+ -MVs preceded each β-score drop along with a concomitant rise in insulin needs, suggesting ß-cell damage or altered function. Significant elevation of liver ASGPR+ -MVs, endothelial CD105+ -MVs, neutrophil CD66b+ -MVs, monocyte CD 14+ -MVs, and T4 lymphocyte CD4+ -MVs occurred before each β-score drop, CD8+ -MVs increased only in F, B lymphocyte CD19+ -MVs remained undetectable. In conclusion, PSA-NCAM+ -MVs are non-invasive early markers of transplant dysfunction, while ASGPR+ -MVs signal host tissue remodeling. Leukocyte MVs could identify the cause of graft dysfunction. This article is protected by copyright. All rights reserved.