Transcatheter aortic valve replacement (TAVR) has rapidly changed the landscape of treatment for severe, symptomatic aortic stenosis (AS). However, since the advent of transcatheter-based therapy, operators have grappled with decisions about access site for valve implantation. While these challenges have diminished with increased procedural experience and technological advances in delivery systems, they remain present, particularly in patients with underlying severe peripheral artery disease (PAD). Given that multiple early studies highlighted the increased mortality and higher rates of adverse procedural events in transapical (TA) compared to transfemoral (TF)-TAVR, most centers have transitioned to a ‘‘femoral first’’ strategy for TAVR access. While analysis using propensity matching attempts to eliminate treatment bias, multiple confounders remain that make TA-TAVR and TF-TAVR patients fundamentally different.