Transcatheter heart valve replacement is a key advancement in the cardiovascular device industry and provides an alternative to open surgical procedures for patients that suffer from severe symptomatic stenosis and/or regurgitation. The functions and boundary conditions of the four heart valves are unique and must be considered separately. It is essential that the structural durability of these high-risk valve replacement implants is thoroughly assessed through testing and analysis. As such, ISO 5840 outlines a comprehensive device durability approach that incorporates worst-case boundary conditions, computational stress/strain analyses, and benchtop fatigue testing. The present study is focussed on 100,000,000-cycle fatigue testing of custom-designed “diamond-shaped” coupons of process-optimized high purity VAR/EBR Nitinol. Benchtop testing was coupled with finite element analysis (FEA) and microstructural characterization to provide an in-depth understanding of durability.