The ONTARGET trial programme tested the effects of the angiotensin AT1 receptor blocker (ARB), telmisartan, alone or in combination with the angiotensin converting enzyme (ACE) inhibitor, ramipril, in more than 25.000 patients at high cardiovascular risk including diabetes on a combined endpoint consisting of cardiovascular death, non-fatal stroke or myocardial infarction and hospitalisation for congestive heart failure. Patient selection and study procedures followed the previous HOPE trial. In the parallel TRANSCEND study, nearly 6.000 patients, all intolerant to ACE inhibition, were subjected to telmisartan or placebo. In ONTARGET, telmisartan proved to be non-inferior to ramipril with respect to the combined primary endpoint and all secondary endpoints, and was better tolerated than ramipril. Combination treatment (dual RAS blockade) was not superior to ramipril (and telmisartan-) treatment but associated with more side effects. In TRANSCEND, telmisartan was not superior to placebo when applying the above combined primary endpoint but was significantly better with respect to the predefined main secondary endpoint corresponding to HOPE, i.e. excluding hospitalization for congestive heart failure. Telmisartan thus proved to be the first and so far the only representative of the ARB class that can be used as an alternative to the “gold standard” ACE-inhibitor, ramipril, in patients at high cardiovascular risk with or without hypertension.