Fatigue of CoCr alloy stents has become a major concern in recent times, owing to cases of prematurefracture, often driven by microstructural phenomena. This work presents the development of a micro- mechanical framework for fatigue design, based on experimental characterisation of a biomedical grade CoCr alloy, including both microscopy and mechanical testing. Fatigue indicator parameters (FIPs) within the micromechanical framework are calibrated for the prediction of microstructure-sensitive fatigue crack initiation (FCI). A multi-scale CoCr stent model is developed, including a 3D global J2 continuum stent-artery model and a 2D micromechanical sub-model. Several microstructure realizations for the stent sub-model allow assessment of the effect of crystallographic orientations on stent fatigue crack initiation predictions. Predictions of FCI are compared with traditional Basquin-Goodman total life predictions, revealing more realistic scatter of data for the microstructure-based FIP approach. Com- parison of stent predictions with performance of a 316L stent for the same generic design exposes the design as over-conservative for the CoCr alloy. In response, the micromechanical framework is used to modify the stent design for the CoCr alloy, improving design efﬁciency.