We describe our preliminary experience with percutaneous renal denervation in end-stage renal disease patients with resistant hypertension and challenging anatomy, in terms of the feasibility, safety, and efficacy of this procedure. Four patients with end-stage renal disease patients with resistant hypertension (mean hemodialysis time, 2.3 years) who had been taking at least four antihypertensive medications underwent percutaneous renal denervation. Renal artery eligibility included the absence of prior renal artery interventions, vessel stenosis <70%, or extended calcifications (more than 30% of the vessel circumference). No cut-off values of vessel diameter were used. All patients were successfully treated with no intra- or postprocedural complications, and all showed 24-hour ambulatory blood pressure reduction at the 12-month follow-up. Percutaneous renal denervation is a feasible approach for end-stage renal disease patients with resistant hypertension with encouraging short-term preliminary results in terms of procedural efficacy and safety.