The aim of the study was to investigate the possibility of increasing the hypotensive effect in patients who did not reach the target blood pressure level in routine outpatient practice by replacing indapamide or hydrochlorothiazide with chlorthalidone in the complex pharmacotherapy regimen, as well as to evaluate the effect of treatment modification on vascular wall stiffness and volemic status of the examined patients. The pilot study included 35 patients with stage I–III hypertension, who received antihypertensive therapy and had not achieved the target blood pressure level at the time of screening. The study design involved replacing hydrochlorothiazide or indapamide with chlorthalidone (Dikardplus) at an initial dose of 12.5 mg/day. During therapy, the dynamics of blood pressure, heart rate, arterial stiffness indices, and volemic status were assessed. Conclusion. The use of chlortalidone in patients with arterial hypertension led to a significant decrease in systolic and diastolic blood pressure (p = 0.000007 and p = 0.015, respectively), achieving the target blood pressure level in the vast majority (n = 27) of patients. There was a tendency to decrease vascular stiffness in patients with arterial hypertension while taking chlortalidone, while no significant changes in volemic status were observed (p > 0.05).