Endomyocardial biopsy is fundamental to the success of cardiac transplantation and can also provide important information for the diagnosis of primary and secondary myocardial pathology. Classically, endomyocardial biopsy procedures have utilized fluoroscopy to guide bioptome manipulation. However, echocardiographic guidance has many distinct advantages. We review our experience of 4301 echocardiography guided endomyocardial biopsy procedures. Our overall major complication rate was 0.4% with one right ventricular perforation and no procedure related mortality. These results compare favorably to traditional fluoroscopic techniques. Echocardiographic guidance for endomyocardial biopsy is safe, effective, and efficient.