Objective: Central systolic blood pressure (cSBP) is considered an important haemodynamic parameter, and a relevant prognostic risk factor. Data about control of cSBP with single-pill combination (SPC) treatment are lacking. Therefore we assessed the effect of perindopril/amlodipine (P/A; dual SPC arm) and perindopril/amlodipine/indapamide (P/A/I; triple SPC arm) in naïve and uncontrolled hypertensive patients on 24-hour cSBP compared to office BP. Design and method: 440 adults with essential hypertension were assessed in the 16-week interventional, open-label, prospective, international, multicentre trial PRECIOUS. ABPM was performed at the baseline and end of the trial (Mobilograph PWA). At inclusion, naïve or patients uncontrolled on previous mono or dual therapy other than P/A were assigned to dual SPC arm with initial dose of 4/5 mg P/A. Patients uncontrolled on previous dual or triple therapy were assigned to triple SPC arm with initial dose of 4/5/1.25 mg P/A/I. If not reaching office BP control, initial dose was up titrated in 4-week intervals to 8/5 mg, 8/10 mg P/A or 8/10/2.5 mg P/A/I in dual SPC arm and to 8/5/2.5 mg or 8/10/2.5 mg P/A/I in triple SPC arm. Results: In 16 weeks mean office BP decreased from 156.3 ± 10.9/98.6 ± 8 mmHg to 128.4 ± 9.4/81.7 ± 7.2 mmHg in dual SPC arm and from 157.9 ± 12.6/97.5 ± 9.5 mmHg to 127.7 ± 11.4/80.3 ± 7.5 mmHg in triple SPC arm. The average cSBP decreased from 132.1 ± 9.4 mmHg to 115.4 ± 8.9 mmHg in dual SPC and from 135.8 ± 11.1 mmHg to 114.7 ± 9.8 mmHg in triple SPC arm. All BP reductions were statistically significant (p < 0.001). 77.7% of patients achieved normal office BP values in dual SPC arm and 82.5% in triple SPC arm. A reduction of cSBP below 120 mmHg was reached by 68.9% of patients in dual SPC and by 71.5% in triple SPC arm. Conclusions: In triple SPC arm, higher proportion of patients reached target office BP which was reflected also in lower cSBP compared to dual SPC arm. This is important information showing the advantageous effect of triple SPC on cSBP. Usefulness of putting cSBP as additive information, reflecting effect of SPC treatment in clinical practice, will need to be proven with longer patients’ follow up.