The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) was a 25,620 patient study program comparing telmisartan with ramipril or the combination thereof in patients at increased cardiovascular risk. Ramipril had previously been proven to prevent cardiovascular events in a similar population within the HOPE-trial. However, ramipril and other ACE inhibitors (ACE-Is) may have limited tolerability that might restrict their use in patients requiring secondary prevention, whereas angiotensin receptor blockers (ARBs) are suggested to be better tolerated. However, no ARB had been compared with the standard treatment, ramipril, in these cardiovascular patients at increased risk. ONTARGET showed that telmisartan was as effective as ramipril in preventing cardiovascular events, but was better tolerated. The combination of ramipril and telmisartan was not superior to either monotherapy. Taken together, ONTARGET demonstrated that telmisartan is as effective as ramipril in a broad cardiovascular increased-risk population in the middle of the cardiovascular continuum. In these patients who are intolerant to ACE-Is or who do not achieve blood pressure control, the ARB with the best evidence for secondary prevention is telmisartan according to the results of the ONTARGET trial.