Background: Despite the disadvantaged position of central adrenergic drugs (CAD) in the current therapeutic regimens of hypertensive patients, we hypothesized that the addition of the most recent representatives of this class - I1-imidazoline agonists (CAD-I1A) - to the usually recommended drugs might contribute to better blood pressure (BP) control. Method: This multicentric observational prospective study included patients with BP . 140/90 mm Hg who were using at least two antihypertensive drugs and were reassessed at three months apart in 44 urban medical centers. Patients with modifications in therapy were subsequently divided into two subgroups: one study group, with CAD-I1A added to the initial therapeutic regimen, and one control group characterized by the addition of a drug from any other class of antihypertensives. Results: The rate of BP normalization was 43% (144/333) after CAD-I1A addition vs 26% (15/58) following any other changes in treatment (p<0.01). The binomial logistic regression has validated the presence of CAD-I1A in the therapeutic regimen (p<0.001) and the stage of hypertension at baseline (p<0.01) as statistically significant predictors of a better BP control, while demographic, socio-economic, lifestyle factors and comorbidities were similarly distributed between the two groups. No differences in the rate of side effects were identified. Conclusions: The results of our study indicate a high probability of BP normalization when a CAD-I1A is added to the therapeutic regimen of patients with uncontrolled hypertension under at least two drugs.