OBJECTIVE: Daily sessions of slow-breathing (6 breaths/min) significantly reduced 24-h ambulatory blood pressure (ABP) in patients with mild hypertension and this effect persisted at least 6 months after the interruption of sessions. The sequence of changes induced by slow-breathing (SB) daily sessions on the modulation of ambulatory blood pressure, renal resistive index, heart rate variability (HRV), and baroreflex sensitivity (BRS) was thus investigated in a randomized, controlled clinical trial. METHODS: Thirty-seven patients (30-75 years, grade I essential hypertension), untreated with antihypertensive drugs, were randomized to daily sessions (30 min) of music-guided SB (<10 breaths/min) (intervention, n = 24) or simple relaxation (control, n = 13). Office and ambulatory blood pressure monitoring renal Doppler ultrasound, assessment of BRS (sequence method and spectral analysis), and HRV (spectral power in the high- and low-frequency bands) were performed at baseline, and after 1, 4, and 8 weeks. Mixed model analysis was conducted on derived variables given by the difference between each measurement and the baseline value within subjects. RESULTS: After 1 week, the intervention enhanced the parasympathetic modulation (high-frequency power; at least p < 0.05 vs both control and baseline) and reduced renal vascular resistance (p < 0.05 for both comparisons); after 1 month, the enhancement of BRS (p < 0.05 for both comparisons at both methods) paralleled a significant reduction in 24 h ABP (p < 0.05 for all comparisons). INTERPRETATION: Repeated daily session of music-guided SB increased parasympathetic modulation and decreased renal resistive index early in the study. These changes were being followed by a positive modulation of BRS and blood pressure reduction.