Fatigue of CoCr alloy stents has become a major concern in recent times, owing to cases of premature fracture, often driven by microstructural phenomena. This work presents the development of a micromechanical 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 J(2) 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. Comparison 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. (C) 2013 Elsevier Ltd. All rights reserved.