Stroke is the second most frequent cause of death in the world and is responsible for about 5 million deaths each year. Several trials have raised the possibility that blocking the renin-angiotensin system (RAS) may be beneficial in patients with stroke. The recently reported Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) study evaluated the effect of lowering blood pressure with the angiotensin receptor blocker (ARB), telmisartan, initiated early after stroke. A total of 80 patients (8.7%) in the telmisartan group and 934 patients (9.2%) in the placebo group had a subsequent stroke, a nonsignificant 5% relative risk reduction in the telmisartan group. Major cardiovascular events occurred in 1367 patients (13.5%) in the telmisartan group and in 1463 patients (14.4%) in the placebo group, a 6% nonsignificant relative risk reduction. The mean follow-up in the PRoFESS study was only 2.5 years, which was too short to assess the impact of treatment on atherosclerotic disease. Stroke prevention aimed at the atherosclerotic process has repercussions on the entire cardiovascular system. The Kaplan-Meier curve of the incidence of major cardiovascular events in PRoFESS has a striking similarity with the Kaplan-Meier curves of Heart Outcomes Prevention Evaluation (HOPE), EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease (EUROPA) and Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) trials for a similar endpoint. It is highly probable that with a longer follow-up, the difference between telmisartan-treated and placebo-treated patients would become significant. In 2008, patients with cardiovascular disease are considerably better treated than 10 years ago. By omitting one class of drugs from the cocktail used for prevention in these high-risk patients (statins, beta-blockers, antiplatelet drugs and angiotensin-converting enzyme inhibitors or ARBs), part of the benefit obtained by the complete treatment will be lost. PRoFESS seems to be a negative trial at first sight, but if considered together with the available data from other clinical trials, it clearly shows that it would be a mistake to withhold drugs that counteract the effect of angiotensin II in patients with stroke or other atherosclerotic disease.