BACKGROUND: Cuff blood pressure (BP) is recommended for guiding hypertension management. However, central BP has been proposed as a superior clinical measurement. This study aimed to determine whether controlling hypertension as measured by central BP was beneficial in reducing left ventricular mass index beyond control of standard cuff hypertension. METHODS: This multicenter, open-label, blinded-end point trial was conducted in individuals treated for uncomplicated hypertension with controlled cuff BP (<140/90 mm Hg) but elevated central BP (≥0.5 SD above age- and sex-specific normal values). Participants were randomized to 24-months intervention with spironolactone 25 mg/day (n=148) or usual care control (n=153). The primary outcome was change in left ventricular mass index measured by cardiac MRI. Cuff and central BPs were measured by clinic, 7-day home and 24-hour ambulatory BPs. RESULTS: At 24-months, there was a greater reduction in left ventricular mass index (−3.2 [95% CI, −5.0 to −1.3] g/m ² ; P =0.001) with intervention compared with control. Cuff and central BPs were lowered by a similar magnitude across all BP measurement modes (eg, clinic cuff systolic BP, −6.16 [−9.60 to −2.72] mm Hg and clinic central systolic BP, −4.96 [−8.06 to −1.86] mm Hg; P ≥0.48 all). Secondary analyses found that changes in left ventricular mass index correlated to changes in BP, with the magnitude of effect nearly identical for BP measured by cuff (eg, 24-hour systolic BP, β, 0.17 [0.02–0.31] g/m ² ) or centrally (24-hour systolic BP, β, 0.16 [0.01–0.32] g/m ² ). CONCLUSIONS: Among individuals with central hypertension, spironolactone had beneficial effects in reducing LV mass. Secondary analyses showed that changes in LV mass were equally well associated with lower measured standard cuff BP and central BP. REGISTRATION: URL: https://www.anzctr.org.au/ ; Unique identifier: ACTRN12613000053729