Background: Oral levonorgestrel has been linked to increased cardiovascular risk, but currently, no information is available on the effect of the levonorgestrel-releasing intrauterine system (LNG-IUS) on endothelial dysfunction. The objective of this study was to assess endothelial function in LNG-IUS users. Study Design: Sixty women underwent insertion of either an LNG-IUS (n=30) as study group or Copper-T intrauterine contraceptive device (TCu 380A intrauterine device) as control group (n=30). In the midluteal phase of menstrual cycle, endothelium-dependent flow-mediated dilatation (FMD) and endothelium-independent dilatation of brachial artery were studied before and after 3, 6 and 12 months of device insertion. We also assessed the correlation of FMD and serum concentrations of estradiol (E-2), progesterone (P) and LNG. Results: With LNG-IUS, there was a nonsignificant decrease in mean FMD of brachial artery (p>.05) compared with the control group at different time points of the study. Before LNG-IUS, reactive hyperemia caused an 8.3%+/- 1.3% increase in brachial artery diameter compared with 7.1%+/- 1.1%, 7.4%+/- 0.9% and 7.5%+/- 0.9% after 3, 6 and 12 months of LNG-IUS (p>.05). The mean +/- SD LNG plasma levels at 3, 6 and 12 months of LNG-IUS application were 228 87, 204 94 and 191 79 pg/mL, respectively. E2 levels were comparable in women of both studied groups. Mean P levels were significantly lower after LNG-IUS insertion compared with before device insertion and with the control group (p<.05) at all study visits. No correlation was found between LNG levels and FMD. Conclusions: A nonsignificant change detected in endothelial function in LNG-IUS indicates that it has no increased cardiovascular risk. (C) 2013 Elsevier Inc. All rights reserved.