Aims: To assess the blood pressure (BP) lowering efficacy of perindopril 4 to 8 mg/day (equivalent to perindopril arginine 5 to 10 mg/day) in patients whose hypertension was untreated or uncontrolled despite treatment with other antihypertensive drugs. Patients and Methods: This is an open-label, multicenter, observational trial conducted in Canadian general practice clinics. Patients (n = 8208; age: 59 ± 13.1 years) with uncontrolled hypertension (i.e. seated BP above 140/90 mm Hg or 130/80 mm Hg in the presence of diabetes, renal disease, or proteinuria) were prescribed perindopril 4 mg/day. Patients who were previously receiving other ACE inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) were switched to perindopril 4 mg/day. At visit 2 (after 14 to 28 days), dosage of perindopril could be increased to 8 mg/day in cases of failure to achieve BP control. Follow-up was over 12 weeks. Results: Perindopril significantly reduces BP among the overall population and the different subgroups as summarized in the table below. One third of patients required uptitration to the high dosage for higher normalization rate. Uptitration to 8 mg provided an additional mean 10.1/5.3 mm Hg BP reduction, which was even greater among severely hypertensive patients (15.1/5.7 mm Hg). Switching previous ACE inhibitor or ARB to perindopril resulted in reduced BP by a further 15.5/7.7 and 15.9/8.2 mm Hg, respectively. Perindopril was well tolerated, including when it replaced treatment with other ACEIs or ARBs. Conclusions: This trial demonstrates that a perindopril-based strategy uptitrated to the maximal dose as required for BP control, significantly reduces SBP and DBP in untreated or uncontrolled hypertensive patients irrespective of their previous treatment. These findings, combined with its proven risk reduction in myocardial infarction, stroke, and death, make perindopril an optimal treatment for a wide range of hypertensive patients.