The postoperative care of the patient undergoing pulmonary endarterectomy presents challenges that occur not only with other types of cardiac surgery but also with significant respiratory system changes related to alterations in pulmonary blood flow. Postoperative mortality associated with this procedure has declined substantially over the years as a consequence of improved evaluative procedures and selective surgical referral, advances in surgical technique, and an understanding of the unique postoperative complications that may occur. However, postoperative acute lung injury and residual pulmonary hypertension continue to represent major causes of mortality associated with this procedure and represent areas where additional investigative efforts are necessary. Here we describe the unique hemodynamic and respiratory changes that occur in the postoperative pulmonary endarterectomy patient and an evidence-based approach to their optimal management.