Aim To study tactics of outpatient physicians in choosing the treatment when the previous double antihypertensive therapy (AHT) fails and to analyze the effectivity of an amlodipine/indapamide/perindopril arginine triple combination (TC).Material and methods The program included 1252 patients with arterial hypertension (AH); the TC group consisted of 992 (79.23 %) patients (38.3 % males; age, 61.6 [55.0; 67.9]); the control group included 260 (20.77 %) patients (37.7 % males; age, 60.6 [53.3; 67.4]). The main inclusion criteria were essential AH, age 18-79 years, insufficient response to previous AHT (clinical systolic blood pressure (SBP) >140–179 mm Hg). The study duration was three months. The following parameters were evaluated: dynamics of clinical and ambulatory BP (BP self-monitoring (BPSM); frequency of achieving the first goal of <140 / 90 mm Hg and the goal of <130 / 80 mm Hg); and changes in glomerular filtration rate (GFR) and quality of life (QoL). Responses to TC were analyzed in groups with different ranges of increased baseline SBP in patients with AH and diabetes mellitus (DM)/impaired glucose tolerance (IGT), overweight or obesity, and chronic kidney disease (CKD, reduced estimated GFR (eGFR <60 ml/min/1.73 m2). Safety was evaluated based on records of adverse events (AEs).Results The TC group had a more severe condition at baseline by clinical parameters and history and had higher baseline BP, which made difficult the intergroup comparison. Nevertheless at three months, the decrease in clinical SBP was more pronounced in the TC group (from 162.1 to 126.8 mm Hg, Δ=35.7 mm Hg) than in the control group (from 157.8 to 128.4 mm Hg, Δ=29.4 mm Hg). 87.8% of patients in the TC group and 81.9 % (р=0.012) in the control group achieved the first BP goal of <140 / 90 mm Hg; 34.3% and 28.2% of patients, respectively, achieved the BP goal of <130 / 80 mm Hg (р=0.055). The more effective SBP control in the TC group was associated with a pronounced BP decrease with higher BP values at baseline, which was also confirmed by an analysis in subgroups with SBP 140–160, 160–180, and >180 mm Hg. The TC treatment was associated with a pronounced antihypertensive effect with respect of BPSM values, improved QoL, and renal function. Significant decreases in BP and achievement of BP goals by a vast majority of patients receiving TC were also observed in subgroups with DM or IGT, overweight and/or obesity, and CKD. AEs were observed during the treatment only in 8 patients (0.64 %), which confirmed good tolerability and high safety of the therapy.Conclusion The study results demonstrated a therapeutic effect of the amlodipine/indapamide/perindopril arginine fixed-dose combination (Triplixam®). This effect was evident as control of clinical BP with any baseline BP level, including different ranges of increased SBP, in AH combined with DM, IGT, obesity, and CKD, which offers advantages over a subjective choice of AHT. TC improved BPSM values, QoL indexes, provided nephroprotection, and was well tolerated.