Progestagen-only contraceptives are often prescribed to women with an increased cardiovascular risk, despite the fact that only few data are available on the effect of these contraceptives on circulating biomarkers of inflammation and endothelial function. In our prospective case-control study, we aimed to investigate the influence of the low-dose etonogestrel-releasing contraceptive implant Implanon on endothelin-1 and cytokine transforming growth factor beta (TGF-beta1), both factors involved in the early phases of atherogenesis. We also were interested in searching for an interrelation between changes in these two parameters and changes in female hormones and plasma lipids. Cases (n=20) were women using Implanon for contraception, and controls (n=20) were females not using hormonal contraception. Baseline blood samples were taken during the early follicular phase of cycle 1 in both groups. A second sample was taken 12 weeks after Implanon insertion or, for controls, in the early follicular phase of cycle 4. In both groups no significant change in endothelin-1 or TGF-beta1 was observed. In Implanon users, cholesterol, high-density lipoprotein, low-density lipoprotein, sex hormone-binding globulin, and testosterone decreased significantly. No correlations were found between endothelin-1 or TGF-beta1 and the investigated parameters. The results suggest that Implanon does not exert a clinically relevant negative effect on endothelin-1 or TGF-beta.