Baroreflex sensitivity (BRS) and heart rate variability (HRV) are potential therapeutic targets. The present study was conducted to assess changes in BRS and HRV after monotherapy with losartan versus that of atenolol in uncomplicated essential hypertension. Thirty subjects with uncomplicated essential hypertension were randomized to receive atenolol 50 mg to 100 mg (n = 15) or losartan 50 mg to 100 mg (N = 15) daily for 6 months. Instantaneous systolic blood pressure (SBP) and heart rate were assessed using servo-controlled infrared finger plethysmography before treatment and at the end of 3 months and 6 months after treatment. The fluctuation in SBP and interpulse interval (IPI) was divided into three specific frequency ranges by fast Fourier transform as high frequency (HF; 0.15 Hz-0.4 Hz), low frequency (LF; 0.04 Hz-0.15 Hz), and very low frequency (VLF; 0.004 Hz-0.04 Hz). The BRS was expressed as (1) SBP-IPI transfer function with its magnitude in the HF and LF ranges and (2) BRS index alpha. The HRV was expressed as total power and power in the LF and HF ranges of interpulse interval. Blood pressure was reduced to a similar extent in both groups. Compared with the baseline, BRS did not improve in both groups at month 3. However, BRS was significantly improved in the losartan group (P < 0.05) but not in the atenolol group at month 6. In addition, BRS was significantly higher in the losartan group than the atenolol group at month 3 and month 6 (P < 0.05). Moreover, heart rate variability was significantly reduced in the atenolol group at month 6 (P < 0.05), but not in the losartan group. The HRV in the losartan group was significantly higher than that in the atenolol group at month 6 (P < 0.05). These findings suggest superior effects of losartan on BRS and HRV than atenolol in uncomplicated essential hypertension, which may be beyond blood pressure reduction/resetting.