OBJECTIVES: Uncontrolled hypertension remains a major problem for health care systems worldwide, being strictly related to a persistently elevated burden of cardiovascular morbidity and mortality. Because of the multifactorial nature of hypertension, most patients require combination therapy to achieve blood pressure (BP) control. This analysis aimed to further investigate the effectiveness of amlodipine/valsartan/hydrochlorothiazide (A+V+H) single-pill combination in lowering the BP of hypertensive patients, previous assessed in an observational study. METHODS: This analysis was based on a data registry collected in a prospective, open-label, observational study conducted in 7132 patients diagnosed with essential hypertension and for whom treatment with A+V+H was indicated according to clinical practice. The observational period was 3 months. Descriptive analysis, hypothesis testing and linear regression models were performed. RESULTS: The reduction in systolic blood pressure (RSP) between baseline and last visit was 23.73±17.51 (mean±SD) while the reduction in diastolic blood pressure (RDP) was 11.34±10.63 mmHg (mean±SD). A t-test showed that both reductions are statistically significant (p<<0.001). Multiple linear regression models were fitted to RSP and RDP, to assess the influence of patients’ characteristics, comorbidities and previous treatment (R = 0.11 and 0.13, respectively). CONCLUSIONS: Although significant, the model covariates were not sufficient to explain the reduction in SP and DP (11% and 13% explained, respectively) found between the baseline and last visit. Since most of the variables known as relevant to characterize hypertension were included in the study, the results allow to conclude that reduction found is mainly explained by the treatment with A+V+H single-pill combination.