Aim. To provide a rationale for the clinical efficacy and safety of prolonged-release indapamide used in the combination therapy of patients with chronic obstructive pulmonary disease concurrent (COPD) concurrent with hypertension. Subjects and methods. Sixty-five patients (50 men and 15 women) with Stages I—IV COPD and grades 1—3 elevated blood pressure (BP) in whom prior antihypertensive therapy had proved insufficiently effective were examined. Results. Prolonged-release indapamide demonstrated a high efficacy in achieving and maintaining goal BP, in normalizing its daily profile, and in reducing increased variability and the rate of morning rise in BP, without negatively affecting the clinical manifestations of COPD, pulmonary ventilatory function, and serum potassium levels. The drug was shown to have additional pleiotropic effects in lowering the activity of inflammatory markers (high-sensitivity C-reactive protein, intercellular adhesion molecules-1) and the level of endothelial dysfunction markers (endothelin-1, sP-selectin). Another commonly clinically used diuretic hydrochlorothiazide was chosen as a compared drug. Conclusion. The high antihypertensive efficacy and additional pleiotropic properties of prolonged-release indapamide that exerts no negative effect on the clinical manifestations of COPD, bronchial patency, and serum potassium levels demonstrate that it is expedient to incorporate prolonged-release indapamide into the combination therapy of patients with COPD concurrent with hypertension.