Factor V Leiden (FVL) is the most common known inherited cause of thrombophilia; it is present in ∼5% of the Caucasian population. This results from mutation of the factor V protein, which is found to have normal procoagulant function in vitro but is resistant to inactivation by activated protein C. We describe the case of a 61-year-old male heterozygote for FVL with diagnosed coronary artery disease scheduled for off-pump coronary artery bypass grafting. Avoidance of antifibrinolytics completely, early administration of antiplatelet agents, heparin infusion 6 h after surgery or starting low molecular weight heparin, early extubation, active limb physiotherapy, use of pneumatic compression pumps, and most important of all early mobilization holds the key for successful outcomes of these patients. A comprehensive care team comprising an anesthesiologist, surgeons, and a hematologist should manage individuals with FVL.