['Renal denervation (RDN) with radiofrequency (RF) is being used to treat resistant hypertension (rHTN). As 15-30% of treated patients are non-responders to RDN, we investigated whether RDN with cryoenergy can serve as a second-line option.', 'Ten non-responder patients (mean age 55 years, six male) with rHTN were treated with cryoenergy for RDN. In order to qualify as non-responders, patients had to show systolic 24 hr ambulatory BP (ABP) ≥150 mmHg (median ABP 183/102 mmHg, median office- based BP [OBP] 191/108 mmHg) despite treatment with ≥4 different antihypertensive drugs (mean 6), and further not show a reduction of systolic ABP ≥10 mmHg at ≥3 months after RDN with RF. The three/six/12-month follow-up (FU) comprised clinical and biochemical evaluation, OBP and ABP measurement. Additionally, at six months, duplex sonography was performed. Cryoablation with a 7 Fr cryoablation catheter (Freezor® Xtra; Medtronic, Minneapolis, MN, USA) was performed in all patients without complications (four applications in both renal arteries, every four minutes, temperature -75°C). At three, six, and 12 months we found a reduction in systolic OBP of -41/-47/-61 mmHg (n=10/7/6; p=0.044 for all), diastolic OBP of -18/-14/-34 mmHg, systolic ABP of -38/-35/-52 mmHg (n=9/7/6, p=0.014 for all), and diastolic ABP of -20/-13/-18 mmHg (p=0.043 for all), respectively. During FU, no complications occurred and the renal function remained unchanged.'] Is renal denervation with cryoenergy as second-line option effective in the treatment of resistant hypertension in non-responders to radiofrequency ablation?