Coronary surgery with diabetes and severe hemophilia B is a challenging situation requiring specific and adequate therapeutic considerations. We herein report the case of a 52-year-old diabetic patient with severe factor IX deficiency and impaired ventricular function, who was scheduled for myocardial revascularization because of exertional angina and recurrent myocardial infarctions following infusions of factor IX concentrate. The patient underwent a successful off-pump direct myocardial revascularization with neither hemorrhagic nor thrombotic complications. Hematological protocols and operative strategies are assessed and discussed.