We report the case of a patient who underwent two cardiopulmonary bypass (CPB) procedures with Orgaran because of heparin-induced thrombocytopenia. A 38 years-old man with ischemic mitral insufficiency was operated for coronary artery bypass and valvular replacement. The CPB was carried out with heparin. Heparin-induced thrombocytopenia occured and was proven immunologically. Two months later, a new valvular replacement was performed because of paravalvular leak due to endocarditis. The Orgaran-CPB protocol was as follows: 5,000 units before cardiopulmonary bypass, 5,000 units in the priming volume, anti-Xa level between 0.9 and 1.1 units/mL, with injection of 1,500 units if necessary, no administration of protamine. One month later, a new valvular replacement was necessary and performed with the same protocol using Orgaran. No bleeding or thrombotic complication occurred. Orgaran is a safe and reliable anti-thrombotic substitute if anti-Xa activity is closely monitored.