A history of heparin hypersensitivity in patients undergoing cardiopulmonary bypass surgery poses the dilemma of which anticoagulant to use. Here, we report the successful use of a heparin challenge test in a 66-year-old female candidate for coronary artery bypass graft surgery with a past medical history of enoxaparin type I hypersensitivity after pulmonary embolism. Challenge and desensitization protocols are effectively used for essential antibiotics in patients with severe infections and/or allergies, or patients with aspirin intolerance requiring revascularization for coronary disease. A successful use of desensitization protocols to unfractionated heparin has been previously described in four patients undergoing cardiac surgery with various schemes. However, our case report indicates that a challenge test may also offer a quick, safe and effective approach in patients with a history of hypersensitivity reactions to heparin with inconclusive diagnostic tests and/or whenever the use of alternative heparins is tricky.