We have previously shown that combined renin-angiotensin system blockade (RB) was less effective than sequential-nephron blockade (SNB) for controlling BP in resistant hypertension (RH). Whether this is accompanied with an improvement in the mechanical properties of large arteries is unknown.Pts with daytime ambulatory SBP/DBP (dASBP/dADBP) >135 and/or 85mmHg, despite 4 week with irbesartan (Irb)+ HCTZ+amlodipine, were randomised to SNB (n=82) or RB (n=82) for 12 weeks. Central pulse pressure (CPP) and carotid-femoral pulse wave velocity (PWV) were measured by aplanation tonometry. High-resolution echotracking system (Walltrack®) was used to measure carotid artery diameter (Dcca), wall thickness (WT), circumferential wall stress (CWS), and stiffness. All parameters were measured at baseline and week 12.Baseline clinical characteristics did not differ between groups. dASBP decreased more in SNB (–19±12mmHg) vs RB (–8±13mmHg, p<10-6), either for CPP [SNB (–12.8±16.9mmHg) vs RB (–1.0±9.3mmHg, p<0.006)] after adjustment on baseline CPP and deltaMeanBP. CCA stiffness and PWV decreased similarly in both groups. Dcca decreased more in SNB (–267±46μm) vs RB (–7.8±39μm, p=0.01) after adjustment on baseline D and deltaASBP. WT did not differ and CWS decreased more in SNB (–15.2±16.5kPa) vs RB (–5.2±12.6kPa, P=0.001).In RH pts, a ttt strategy based on SNB improved CPP to a greater extent than a RB strategy. This may lead to a better target organ damage prevention and CV outcome. SNB improved CWS. Whether this effect is due aldosterone blockade or sodium depletion remains to be investigated.