The use of large animals in research provides a unique bridge between preclinical findings and clinical relevance, offering a valuable perspective for advancing our understanding of the complexities of heart failure. Multiple models of heart failure have been established with advantages and limitations of each model. Many insights have been gained from these models for understanding both pathophysiological mechanisms and therapeutic interventions for heart failure. We have developed a chronic model of heart failure with reduced ejection fraction in sheep using the coronary microembolization technique. These animals gradually develop heart failure over a period of 3 months. In this chapter, we document how this model can be established. The left main coronary artery is cannulated under fluoroscopic guidance, and polystyrene latex microspheres are injected into the artery. Up to three sequential selective microembolizations are undertaken over a period of 3 weeks. Changes in ECG are monitored, and echocardiography is used to check on the progression of left ventricular dysfunction. All animals were followed for 3 months after the first embolization, and heart tissue was examined to check for changes in cardiac myocyte size. All animals developed stable signs of HF. We propose that multiple sequential intracoronary microembolizations can induce stable myocardial dysfunction with hemodynamic signs of chronic heart failure.