Background: Few studies have examined the safety and efficacy of transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS) in Australian patients. SOLACE-AU was a single-arm, open-label clinical trial conducted in Australian hospitals to determine the safety, performance, and cost implications of TAVI in patients with severe, symptomatic AS at intermediate surgical risk. Methods: This was a prospective, pragmatic, single-arm, multi-center, observational trial of 199 patients with severe, symptomatic AS treated with transfemoral TAVI using the SAPIEN XT transcatheter heart valve (THV) at 11 hospitals in Australia. The primary outcome was Valve Academic Research Consortium-2 (VARC-2) criteria – a composite of seven safety endpoints. Kaplan–Meier (KM) estimates and descriptive analyses were used to evaluate the impact of transfemoral TAVI on safety and valve performance. We also evaluated patient health-related quality of life (QoL) and healthcare resources used throughout the trial. Results: The valve was successfully implanted in 88% of patients. The VARC-2 outcome at 30 days was 12.1% (95% CI: 8.3–17.5%), and almost 90% of patients had improved heart failure symptoms at 1 year based on New York Heart Association functional class criteria. Patient QoL remained stable over time, with mean EQ-5D-3L scores being 0.71 ± 0.20 at baseline and 0.71 ± 0.21 at 2 years. Duration of post-procedure hospitalization (mean: 6.9 ± 4.7 days) decreased as procedural familiarity increased. The median total cost of TAVI decreased 10.1% at 3 years after introduction of the procedure at the sites. Conclusions: The SOLACE-AU trial demonstrated favorable safety and performance of the SAPIEN XT valve in patients with AS at intermediate risk of surgical complications.