Background: Recent trials have confirmed the safety and efficacy of catheter-based renal denervation (RDN) as nonpharmacological treatment in resistant hypertension in the presence of concomitant antihypertensive therapy. Aim: we report data of preliminary experience with RDN (Symplicity Spyral renal denervation system, Medtronic Inc.) in patients with resistant hypertension and high risk condition (previous myocardial infarction treated with myocardial revascularization). Methods: We analyzed 4 patients (3 M/1 F) mean aged 72±7 years, with resistant hypertension (treated at least with 4 antihypertensive drugs, including a diuretic, at maximally tolerated doses, without reaching the therapeutic target) who were previously scheduled in follow up (FU) program, after myocardial revascularization, and treated applying radiofrequency energy for blood pressure (BP) lowering. All participants had baseline assessments before RDN and repeat assessment at 3 months including medical history, automated office BP measurement, and routine blood and urine tests. We analyzed changes between baseline and at 3 months. Statistical Analysis: Normally distributed variables are presented as mean ± standard deviation (SD) and were compared by Student’s t-test for paired data. A p≤0.05 value was considered statistically significant. Results: The antihypertensive drugs used were as follows: beta-blockers, alfa-blockers, calcium channel blockers, angiotensin II receptor antagonists, ACE inhibitors, loop diuretics, thiazide diuretics, canreonate. A total of participants completed FU post-procedure. At 3 months, compared with baseline, systolic BP was reduced by −44,25±13,25 (from 170,75 ± 7,22 to 126,5 ±12,0) mmHg (P<0.005) and diastolic BP reduced by −13,25±7,69 (from 85,75± 7,22 to 72,5 ±6,45) mmHg (P<0.029). Renal function assessed by estimated glomerular filtration rate did not change statistically significantly, from 64.25 ± 6,5 to 62,5 ± 6,7 mL/min per 1.73 m2 (P<0.066). Mean heart rate remained unchanged. At 3 months, participants were taking at least one less antihypertensive drug than at baseline (from 5 ± 1 to 3 ± 1) (P=0.006). Conclusions: RDN results in a significant and robust reduction in both office and ambulatory systolic and diastolic BP at 3 months FU after catheter-based RDN on less medication and without evidence of adverse consequences on renal function.