OBJECTIVE: Our aim was to investigate medium-term effects of device-guided breathing on blood pressure (BP) and its capacity to improve the cardiovascular autonomic balance in hypertensive diabetic patients. This feasibility study was conceived as a proof-of-concept trial under real life conditions for justification of further investigations. METHODS: A randomized, controlled study (RCT) of the effects of device-guided slow breathing on top of usual care against usual care alone (including non-pharmacological and pharmacological treatment). The intervention included 12-min sessions of guided breathing performed daily for 8 weeks. Treatment effects were assessed with ambulatory blood pressure monitoring (24h ABPM) and with spectral analysis of short-term heart rate variability (HRV) obtained during standardized modified orthostatic load. Thirty-two subjects with diabetes and antihypertensive therapy were randomly assigned to both study groups. RESULTS: After 8 weeks of guided breathing, significant reductions were demonstrated in 24 h systolic BP (x+/-SEM: 126.1+/-3.0 vs 123.2+/-2.7 mmHg, p=0.01), and in 24 h pulse pressure (PP, 53.6+/-2.6 vs. 51.3+/-2.5 mmHg, p=0.01), whereas no significant impact in the control group was shown. The differences in treatment effects (delta mmHg, RESPeRATE(R) vs control) were significant only for PP (-2.3+/-0.8 vs +0.2+/-1.2 mmHg, p<0.05). Strong baseline dependence of treatment effects (delta systolic BP) was observed (p<0.01). Guided breathing showed a stronger treatment effect in terms of an increase in HRV, predominantly in low frequency band (p<0.03 vs. usual care). CONCLUSION: Even in well controlled hypertensive diabetic patients, guided breathing induced relevant effects on BP and HRV, finding which should be investigated further.