Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug reaction characterized by thrombocytopenia and a high risk of thrombosis. Patients with HIT and a need for cardiac surgery with cardiopulmonary bypass represent a challenging group, as anticoagulation with unfractionated heparin (UFH) is the primary treatment choice. We conducted a systematic review evaluating intraoperative anticoagulation strategies for patients with a history of HIT who required cardiac surgery with cardiopulmonary bypass. Guidance statements were generated through consensus of the writing group. Of 1732 screened articles, 30 studies were included. Strategies evaluated were (1) direct thrombin inhibitors; (2) UFH after preoperative or intraoperative therapeutic plasma exchange (TPE); (3) UFH in combination with a potent antiplatelet agent; and (4) heparin reexposure in patients with negative functional assays. Of these, bivalirudin has the strongest supporting data and appears effective; still, its association with increased bleeding and practical limitations, including a lack of a reversal agent, limit its use. TPE with or without intravenous immunoglobulin reduces antiplatelet factor 4/heparin antibody titers and allows for intraoperative UFH use, although protocols are heterogeneous. Use of potent antiplatelet agents with UFH reexposure show promise but carry risks of bleeding and hypotension. Thus, alternative strategies of using UFH in combination with TPE or potent antiplatelet agents may be considered on a case-by-case basis. For patients with negative functional assays, evidence suggests that limited intraoperative UFH reexposure carries a low risk of HIT recurrence, provided postoperative monitoring is performed. These guidance statements provide a framework for multidisciplinary decision making in a complex clinical scenario.