BACKGROUND Perindopril is a tissue-specific ACE inhibitor with 24 hours long blood pressure-lowering effect, which protects blood vessels and decreases the variability of blood pressure. OBJECTIVE The aim of our study was to investigate the effectiveness and safety of perindopril in newly diagnosed or previously treated but uncontrolled adult hypertensive patients. METHODS This prospective cohort study included primary care patients with essential hypertension. Primary study outcomes were decreasing arterial blood pressure to normal levels (<140/90 mmHg), reducing systolic arterial blood pressure for 10 mmHg or more and reducing diastolic arterial blood pressure for 5 mmHg or more. Safety was evaluated by type and frequency of adverse events. RESULTS In the great majority of the study patients (more than 96%) perindopril was effective as monotherapy, achieving a significant reduction in both systolic and diastolic blood pressure, and in three-quarters of the study patients it normalized both systolic and diastolic blood pressure. The effectiveness of perindopril was shown in both patients with previously and newly diagnosed hypertension, adverse events were mild and rare, even hyperkalemia was encountered less often than before the onset of the therapy with perindopril. CONCLUSIONS Our study confirmed excellent effectiveness of perindopril in the treatment of essential hypertension and its remarkable safety. When used as monotherapy of hypertension, perindopril's doses should be carefully titrated until the achievement of full effect, which in some patients should be awaited for at least 6 months from onset of the therapy.