The effects of cardiopulmonary bypass on patients who have active or dormant malaria are unknown. What is known is that malaria-induced hemolysis can be exacerbated by cardiopulmonary bypass. We report 3 cases in which patients with active or dormant malaria underwent open-heart surgery. Two of them received quinine prophylaxis, and the 3rd patient (who presented with an active infection) received longer-term preoperative treatment with quinine. In all 3 cases, the surgery was performed uneventfully. We suggest preoperative quinine prophylaxis for patients with a history of malaria whose blood smears are negative for parasites, and we advocate more radical preoperative treatment with quinine for patients whose blood smears are positive at presentation. These measures appear to prevent hemolysis and fever during both the preoperative and postoperative periods. However, there is need of a multicenter study to ascertain the actual effects of cardiopulmonary bypass on patients with malaria.