BACKGROUND Angiotensin-converting enzyme inhibitors (ACE-Is) benefit patients with cardiovascular disease (CVD), but they are complicated by intolerance (in up to 20%) and incomplete suppression of the renin–angiotensin system (RAS). Angiotensin II receptor blockers (ARBs) show superior tolerability to ACE-Is and have effective BP lowering, renal protection and cardioprotection effects, but their role in CVD prevention is less well defined. METHODS: The ONTARGET Trial Programme is an academic-industry collaboration on two parallel studies. ONTARGET is a double-blind, randomised trial to compare the efficacy and safety of the combination of the ARB telmisartan 80mg daily and the ACE-I ramipril 10mg daily with their respective monotherapies in the prevention of stroke, myocardial infarction, CVD death, and hospitalization for cardiac failure. TRANSCEND will compare the efficacy of telmisartan against placebo in ACE-intolerant patients. Other aims of both trials include investigation of treatment on diabetes, renal failure, dementia and atrial fibrillation. Patients (age 55 yrs or more with increased CVD risk (history of coronary artery disease, stroke/TIA, peripheral vascular disease, or diabetes with end-organ disease) are recruited from over 700 centres in 40 countries. The studies are coordinated from McMaster, Auckland and Oxford Universities, and by the sponsor, Boehringer Ingelheim, Germany. RESULTS: Over 18 months to July 2003, 25,620 patients (av. age 66 yrs; 73% male) were randomised into ONTARGET. Their medical history includes myocardial infarction (in 49%), stroke/TIA (20%) and hypertension (68%) which was an ACE-I in 57%. Only 11% of potentially eligible patients failed to be randomised after the active one month run-in phase, due mainly to poor adherence or patient reluctance, which is comparable to other major CVD trials such as HOPE and PROGRESS. Recruitment continues into TRANSCEND. CONCLUSIONS: The ONTARGET Trial Programme is the most comprehensive evaluation of ARB therapy in CVD prevention to date. Patient follow-up continues for the next 4 years.