The plant derived triterpene ursolic acid (UA) has been intensively studied in the past; mainly as an anti-cancer compound and for its cardiovascular protective properties. Based on the controversy of reports suggesting anti-angiogenic and cytotoxic effects of UA on one side and cardiovascular and endothelial protective effects on the other side, we decided to assess UA effects on primary human endothelial cells in vitro and atherosclerotic plaque formation in vivo.Our in vitro analyses clearly show that UA inhibits endothelial proliferation and is a potent inducer of endothelial cell death. UA causes DNA-damage, followed by the activation of a P53-, BAK-, and caspase-dependent cell-death pathway. Oral application of UA in APO E knockout mice potently stimulated atherosclerotic plaque formation in vivo, which was correlated with decreased serum levels of the athero-protective cytokine IL-5.Due the potent endothelial cell death inducing activity of UA, a systemic application of UA in the treatment of cardiovascular diseases seems unfavourable. UA as an anti-angiogenesis, anti-cancer and – locally applied – cardiovascular drug may be helpful. The DNA damaging activity of UA may however constitute a serious problem.