OBJECTIVE: To investigate the sex differences in the efficacy of renal denervation (RDN) in patients with resistant hypertension (RHT) concerning the size of abdominal fat depots, changes in biomarkers of sympathetic activity, and renal function. MATERIALS AND METHODS: 24 men (56.5 ± 7.8 years) and 33 women (59.5 ± 8.4 years) with RHT were enrolled in the study and underwent RDN. 24-h ambulatory blood pressure (BP) [systolic/diastolic (SBP/DBP)], serum creatinine (with eGFR calculation), serum adipocytokines (leptin, adiponectin, resistin), serum metanephrines and normetanephrines were measured baseline and 12 months after RDN. The size of subcutaneous, visceral, and perirenal adipose tissue (SAT, VAT, and PRAT) was assessed using MRI. RESULTS: After RDN, BP decreased, leptin increased, and adiponectin, resistin, and metanephrine levels did not change in both sexes. There was a decrease in normetanephrine levels in women and a similar trend in men. In men, the eGFR did not change. In women, the eGFR remained unchanged only in those with chronic kidney disease (CKD) ( CONCLUSIONS: The magnitude of the antihypertensive effect of RDN depends on signs of visceral obesity and, in men, also on the presence of CKD. Renoprotective effects of RDN in men are obtained regardless of the initial kidney function, while in women, it was observed only in individuals with CKD. Additional beneficial effects of RDN in women include a decrease in normetanephrine levels and a reduction in PRAT size.