Background The aim of the study was to evaluate whether the combined treatment of calcium channel blocker, amlodipine and β-blocker, betaxolol, favorably affects cardiac autonomic nervous activity (CANA) and health-related quality of life (HRQL). Methods and Results A total of 65 patients with a poor blood pressure (BP) control with a low dose amlodipine therapy were randomly assigned to the amlodipine dose-up group (n=21) and betaxolol adding group (n=44). Before and after a 6-month treatment, BP, heart rate variability (HRV), HRQL and blood chemistries were evaluated. Low frequency (LF) spectra/high frequency (HF) spectra and HF/total power spectra (TP) were calculated as indexes of CANA, and HRQL was assessed by the questionnaire sheets. BP was well controlled in all patients of the present study. In the betaxolol adding group, LF/HF decreased (2.1±1.9 to 1.3±0.9, p<0.05) and HF/TP reciprocally increased (0.41±0.17 to 0.52±0.18, p<0.05), whereas the amlodipine dose-up group showed no significant changes in the HRV. HRQL was significantly improved in the betaxolol adding group, whereas it remained unchanged in the amlodipine dose-up group. Blood chemistries remained unchanged except for the slightly increased plasma brain natriuretic peptide concentrations in the betaxolol adding group (36±47 to 62±62 pg/ml, p<0.05). Conclusions Combined treatment of amlodipine and betaxolol appears to be more useful than amlodipine dose-up therapy, because combined treatment improves CANA and HRQL. (Circ J 2008; 72: 764 - 769)