BACKGROUND Malaria is the infection caused by inoculation with the mostly obligate intraerythrocytic protozoa of the genus Plasmodium. Severe malaria manifests as multiple organ dysfunction with high parasitemia counts characterized by coma, stupor, and severe metabolic acidosis. Physicians in the United States do not frequently encounter patients with malaria, and the drugs are only available through the Centers for Disease Control and Prevention, which makes the management of this disease somewhat complicated. In 2019, the marketing of quinine for malaria was discontinued. In May 2020, the US Food and Drug Administration approved the use of intravenous artesunate for the treatment of adults and children with severe malaria. This case report describes a case of Plasmodium falciparum malaria in a 55-year-old woman who returned home to Florida from a visit to Ghana. CASE REPORT A previously healthy 55-year-old woman with no significant past medical history presented to the Emergency Department (ED) of a hospital in south Florida due to cyclic fever for 7 days. The patient's family reported mental status changes since symptom onset. The patient had returned from a 10-day trip to Ghana 18 days prior to admission. On arrival to the ED, the patient appeared lethargic and within hours was in respiratory distress. She was intubated and mechanically ventilated in the ED for acute hypoxemic respiratory failure. A malaria smear was positive with 25% parasitemia, and a diagnosis of severe malaria was made, consistent with P. falciparum infection complicated by multi-organ failure. Infectious disease consultation was obtained and an infusion of intravenous (IV) quinidine and IV doxycycline was emergently started due to the anticipated delay in obtaining artesunate. During the second day of admission, the patient had QTc prolongation, so quinidine was switched to IV artesunate. The parasitemia and acidosis started improving by the third day of therapy. CONCLUSIONS Given that artesunate is more effective, easier to dose, and more tolerable than quinidine, it is now the treatment of choice for severe malaria in the United States.