Centrally acting antihypertensive agents of second generation are imidazoline I1-binding agents, which fulfil the requirements of modern antihypertensive drugs. Rilmenidine (Tenaxum, Servier) has the highest affinity to I1- receptors and by this way effectively decreases the activity of sympathetic nervous system. In our present study, 1322 newly diagnosed hypertensive patients (57.5 ± 12.0 years of age) with overweight or obesity were observed. Rilmenidine therapy (up-titrated, 1 mg 1-2 x daily) was found to be effective and safe. After 3 months of therapy, the significant BP and heart rate (HR) reduction was achieved: SBP from 154.9 ± 13.3 to 134.4 ± 10.8 mmHg, DBP from 93.6 ± 7.8 to 82.2 ± 6.8 mmHg, HR from 80.5 ± 9.2 to 74.0 ± 7.2 beats per min (P < 0.001, respectively). Besides this, a significant decrease of BMI (P < 0.001), waist circumference (P < 0.001), quality of life improvement (P < 0.001), decrease of glycaemia (P < 0.001), total cholesterol level (P < 0.001), LDL cholesterol (P < 0.01), triacylglyceroles (P < 0.01) and decrease of sympathetic hyperactivity (P < 0.001) according to Opavsky questionnaire was observed. This reduction was evident also in all the sub-groups according to the gender and co-morbidities: metabolic syndrome, abdominal obesity, dyslipidemia, fasting glycaemia > 5.6 mmol/l, diabetes mellitus, perimenopausal women (P < 0.001, respectively). During the study, no patients withdrew from treatment because of serious side effects. The results showed the advantages of rilmenidine (Tenaxum) in complex treatment of overweight/ obese hypertensive patients or within metabolic syndrome.