The new ASTM F3211, Standard Guide for Fatigue-to-Fracture (FtF) Methodology for Cardiovascular Medical Devices, has recently been published, outlining the need for testing a device beyond physiological loading conditions. Fatigue-to-fracture is an engineering technique that allows for the prediction of failure mode, location of failure sites, and expected lifetime without the need to do long-term testing. Clinical stent fractures have been reported, and the FtF methodology helps us to understand and optimize a stent design and to assess the influence of material and process variations in an iterative approach combined with finite element analysis. Fatigue-to-fracture testing of superelastic Nitinol can be performed relatively easily because hyperphysiological loading will not cause imminent failure. However, conventional coronary stent materials such as cobalt-chromium alloys, usually being tested under radial physiological loading, are posing a challenge. If larger deformations are applied, samples will be deformed permanently in the initial load cycles and, in the case of radial loading, a constant deformation history over useful test durations is difficult to achieve. In this work, a fatigue durability tester capable of delivering testing pressure up to 2,500 mmHg at pulse frequencies up to 60 Hz was developed, allowing for hyperphysiologic loading of implanted, coronary stents. With this instrument, the adjustable variable could be magnitude of pulsatile pressure, or device deflection. Various sample preparation techniques were evaluated to force the stents to large cyclic radial deformations without compromising initial structural integrity. The most promising approach was found to be the embedding of implanted stents with a very thin silicone layer. This allows for isolating the loading to expansion only, compression only, or both expansion and compression per cycle. A high-speed camera and tracking software were used to monitor deflections at predetermined locations within the stent design to match finite element analysis models and simulation to achieve the desired loading history.