Aim. To evaluate the impact of combination antihypertensive therapy with ekvator on heart rate variability (HRV) parameters and target organ status in patients with arterial hypertension (AH) and type 2 diabetes mellitus (T2DM). Subjects and methods. The investigation enrolled 30 patients aged 40-65 years with Stages II-III AH concurrent with T2DM. All the patients received combination antihypertensive therapy with amlodipine + lisinopril for 12 weeks. HRV parameters, baseline autonomic tone, and autonomic responsiveness were studied, by analyzing ECG reading of their hearts in the 5-minute segments. Echocardiography was performed and arterial elastic properties and renal functional were examined. Results. 12-week ekvator therapy showed a high (93.3%) rate of achieved goal blood pressure (BP) levels. There was a statistically significant reduction in resting tension index by 66% and during an active orthostatic test by 43.5% during combination antihypertensive therapy with amlodipine and lisinopril. Twelve weeks after treatment, the normal type of autonomic responsiveness was prevalent (53.4%) in patients with AH and T2DM, with a significant decline in the number of persons with asympaticotonic autonomic responsiveness. There was a significant decrease in left ventricular mass index by 10.7% and microalbuminuria by 27.7% and a 30% decline in the number of patients with a higher pulse wave velocity along the elastic arteries. There were close highly significant correlations between the parameters of HRV and the status of target organs (heart, kidney, and vessels). Conclusion. 12-week ekvator treatment not only normalizes effectively BP and has a favorable impact on target organs, but also improves HRV parameters in the patients with AH and T2DM, in this connection, HRV may be, in our opinion, regarded as another combination antihypertensive therapy target.