Abstract Background A novel pressure-regulated deployment method for balloon-expandable transcatheter heart valves (THVs) has been developed(1) to improve clinical outcomes by regulating maximal annular wall tension during prosthesis expansion – to both optimise prosthesis-annulus apposition and diminish annular injury. The previous feasibility study(1) showed that THV deployment at wall tensions between 3-3.5 MPa may be associated with reduced paravalvular-leak (PVL) severity and avoidance of annular rupture. Objective To prospectively evaluate the safety and efficacy of the pressure-regulated THV deployment strategy. Methods 341 consecutive patients with severe native aortic stenosis and moderate-severe surgical risk who underwent TAVI with Sapien 3 THVs using a pressure-regulated deployment strategy were included. Target (maximal) deployment pressure was adjusted according to valve size: 5 atm for 29mm, 5.5 atm for 26mm and 6.25 atm for 23mm THVs. Key procedural and clinical outcomes were recorded and analysed using uni- and multi-variate analyses. Results The average patient age was 82.1±6.9 years and 28.2% were female (see attached table). 29.3% had moderate-severe subannular calcification and 14.5% had estimated ≥20% THV oversizing based on TAVI CT. 112 patients (32.8%) were considered at high-risk of annular rupture(2). Post-dilatation rate was 8.2% and was independently associated only with the degree of THV oversizing (OR 3.5, p=0.007, for ≤5% oversizing). On TTE prior to discharge, 85.6% had none/trivial PVL and 14.4% had mild PVL with no observed moderate/severe PVL. Mild PVL was independently associated with age (OR 1.07, p=0.02, per year) and degree of THV oversizing (OR 2.4, p=0.02, for ≤5% oversizing). Resulting THV mean gradient on TTE was 9.7±3.5mmHg overall, with similar results between 23mm (10.5±3.2mmHg) and 26/29mm valves (9.6±3.5mmHg, p=0.2). New PPM rate was 9.6% and was independently associated only with pre-existing RBBB (OR 13.5, p<0.001). New LBBB rate was 11.2% was independently associated only with low THV implantation depth (OR 4.3, p=0.009, for ≤60% of THV length above native aortic annulus). There were no cases of aortic/annular rupture. Conclusions The pressure-regulated strategy for balloon-expandable THV deployment is associated with an excellent safety and efficacy outcomes profile. Notably, there was no significant difference in valve haemodynamics and degree of PVL post-implantation between the smaller (23mm) and larger (26/29mm) THV sizes. These findings suggest that standardisation of THV deployment pressure to achieve target wall tension results in improved haemodynamics, particularly in small-sized valves.Main Table (Truncated)PVL and MG according to THV size