BACKGROUND: Compared with Caucasians, African Americans have lower heart rate variability (HRV) in the high-frequency domain, but there are no studies in blacks born and living in Africa. METHODS: In the Newer versus Older Antihypertensive agents in African Hypertensive patients trial (NCT01030458), patients (30-69 years) with uncomplicated hypertension (140-179/90-109 mmHg) were randomized to single-pill combinations of bisoprolol/hydrochlorothiazide (R) or amlodipine/valsartan (E). 72 R and 84 E patients underwent 5-min ECG recordings at randomization and 8, 16 and 24 weeks. HRV was determined by fast Fourier transform and autoregressive modelling. RESULTS: Heart rate decreased by 9.5 beats/min in R patients with no change in E patients (- 2.2 beats/min). R patients had reduced total (- 0.13 ms(2); p = 0.0038) and low-frequency power (- 3.6 nu; p = 0.057), higher high-frequency (+ 3.3 nu; p = 0.050) and a reduced low- to high-frequency ratio (- 0.08; p = 0.040). With adjustment for heart rate, these differences disappeared, except for the reduced low-frequency power in the R group (- 4.67 nu; p = 0.02). Analyses confined to 39 R and 47 E patients with HRV measurements at all visits or based on autoregressive modelling were confirmatory. CONCLUSION: In native black African patients, antihypertensive drugs modulate HRV, an index of autonomous nervous tone. However, these effects were mediated by changes in heart rate except for low-frequency variability, which was reduced on beta blockade independent of heart rate.