Background: Glycemic outcomes have been noticeably improved by algorithms for automation of insulin delivery but effects of those systems on diabetes complications has not yet been established. Aim: To investigate the effects of advanced hybrid closed loop (AHCL) vs sensor augmented pump with predictive low glucose suspend (PLGS) on glucose control and early biomarkers of microvascular damage in a cohort of type 1 diabetes (T1D) patients. Methods: This is a multicenter, open-label, randomized, parallel-group trial (NCT05477030). 48 adults with long-lasting T1D previously treated with continuous subcutaneous insulin infusion were randomized 1:1 to use Minimed™ 780G system in AHCL or PLGS mode. Glycemic outcomes and circulating endothelial progenitor cells (EPCs; CD34⁺ KDR+/CD133+ cells) were assessed at baseline and at 26-weeks. Continuous variables are presented as means with standard error means. T-test was performed to compare continuous variables; the Pearson correlation coefficient was used for correlation analyses. Values <0.05 were considered statistically significant. Results: after 6 months, better glycemic metrics were found in AHCL vs PLGS, with time in range 79±1.4 vs 65±2.5% (p<0.0001), time in tight range 55±1.8 vs 36.7±2.4% (p<0.0001) and HbA1c 50±1.5 vs 56±1.7 mmol/mol (p<0.005). No severe adverse events occurred in both groups. Moreover, a decrease in EPCs number in PLGS but not in AHCL was observed at 26-weeks (Δ-221±61 vs -1.7±72 cells/ml respectively, p<0.05), with a positive correlation between time in range and time in tight range at 6 months and EPCs count change (r=0.37, p<0.01; r=0.31, p<0.05). Conclusion: A six-months use of an advanced automated insulin delivery system led to a significant improvement in glucose control and seemed to stabilize EPCs count overtime, suggesting potential effects on the vascular endothelium.