Background and Objectives: Hypertension is the leading cause of death with 10,4 million deaths and 218 disability adjusted life years (DALYs) worldwide in 2017. Despite GDMT, about 10 to 20% of hypertensive subjects will be poorly controlled, meeting the definition for difficult to treat (DTTH) and refractory hypertension (RH). Renal denervation (RDN) with Spyral Simplicity SystemTM has become a promising nonpharmacological treatment for DTTH and RH, and it has shown to be an effective and safe procedure for RH patients in randomized clinical trials with up to 12 months follow-up. Methods: This is a single-center registry including 6 adults with DTTH and RH confirmed by ABPM and without secondary hypertension, underwent RDN in a tertiary hospital in Bucaramanga, Colombia. A 6-months follow-up was performed, recording clinical data (symptoms, NYHA functional class, number and type of antihypertensive medications, heart rate and ER visits) and paraclinical tests (ABPM, eGFR and echocardiogram). Results: Mean age was 73 ± 4,64 years-old with 50% females. Main comorbidities were dyslipidemia (100%), cardiovascular disease (100%), and type 2 diabetes (83,3%). Pre-procedural medication average was 5. All patients were in NYHA II, with preserved left ventricular EF and mild to moderate diastolic disfunction. At 6 months of follow-up, there was a mean reduction in systolic blood pressure (SBP) of 10 mmHg (145 to 135 mmHg) in ABPM and 26 mmHg (169 to 143 mmHg) in office. There were not significant changes between pre- and post-procedural mean HR (68 vs. 61 bpm), neither short- or long-term complications associated with the procedure. In average, one drug withdrawal was observed. All the subjects improved their NYHA functional class. There were no ER visits in the 6-month follow-up. Conclusions: RDN is effective and safe for patients with DTTH and RH, achieving significant reduction in ABPM and office SBP, reducing medication number, improving NYHA functional class and avoiding visits to ER in the mid-term follow-up.