Objective. Renal sympathetic denervation (RDN) is one of the invasive treatment options for the patients with hypertension (HTN) who are resistant to antihypertensive therapy (AHT). The short-term efficacy of RDN has been proven in a number of randomized clinical trials, but remains controversial, the data on its long-term efficacy are limited. The aim of our study was to evaluate the natural course of HTN, to assess long-term major adverse cardiovascular events (MACE) and other outcomes, as well as AHT efficacy and its features in patients with resistant HTN after bilateral RDN during extended prospective follow-up. Design and methods. We included 22 patients with truly resistant HTN (median 57 y. o., 9 males), in whom RDN was performed during 2012–2015 in the clinical center of excellence. We assessed initial and further (after 1 year and after ≥ 5 years) clinical, laboratory and anthropometric parameters, as well as detailed AHT history. Long-term MACE and other clinically significant outcomes were recorded. At baseline and follow-up, the quality of life (QoL) was determined with the use of EQ-5D questionnaire at all time points. Multiple linear regression was used to find possible predictors of the efficacy of RDN. Results. A significant and sustained drop in office and ambulatory systolic blood pressure (SBP) and diastolic blood pressure (DBP) was observed at 12 months after RDN compared to baseline values (∆ –24 and –12 mm Hg, p < 0,005; ∆ –10 and –7 mm Hg, p < 0,05, respectively). There were 7 patients with office SBP on-target, and 12 patients were considered responders (∆ SBP > 10 mm Hg). These numbers increased to 10 and 14 patients after ≥ 5 years after RDN. A causal relationship between changes in office SBP was found only for the baseline SBP (β -0,6, p = 0,02). No differences in the number of medications were noted during follow-up (4,4; 4,1 and 4,1 drugs, p = 0,41). During the follow-up 10 MACE occurred and 5 patients were diagnosed with various types of cancer; there were no fatal outcomes. The QoL significantly improved a year after RDN (+9,7 points, p = 0,01), however, a negative trend was observed in the next 5 years with return to reference level. No association was observed between BP and QoL changes at two timepoints. Conclusions. The RDN shows a pronounced clinical effect in patients with resistant HTN up to 5 years, and is not accompanied by an AHT intensification, but is not associated with QoL changes. The initial positive trend for QoL completely harked back after 5 years which may be associated with the development of MACE. The only predictor of RDN positive effect is baseline SBP level.