Background: Hydroxychloroquine (HCQ) is used primarily in the treatment of certain inflammatory disorders and for prevention and treatment of malaria. Overdose may result in altered mental status, seizures, coma, and quinidine-like cardiotoxicity. Intravenous fat emulsion (IFE), an antidotal therapy with proposed but not clearly elucidated mechanism of action, has been used in many overdose scenarios in both human case reports and animal studies but has not been used with success in the context of HCQ exposure. We report a case of hydroxychloroquine overdose treated successfully with IFE along with other standard therapies. Case report: A 51-year-old woman presented to a rural emergency department (ED) 1 . 2 hours after ingesting 35 oxycodone/acetaminophen 5/325 mg tablets and 60 HCQ 200 mg tablets. The patient was drowsy with a blood pressure (BP) of 80/44 mmHg. She received naloxone, epinephrine (EPI) at 0.25 mcg/kg/min, and diazepam 150 mg. She was intubated and transferred by helicopter to a tertiary care center. En route the patient had a ventricular fibrillation arrest that resolved with 10 chest compressions. Upon tertiary ED arrival, the patient had repeated systolic blood pressures (SBP) in the 70's despite her EPI drip. A bolus of 20% IFE 100 mL was given with immediate hemodynamic improvement; within 5 minutes her BP rose to 115/66. EPI was weaned to 0.15 mcg/kg/min within 8 minutes of IFE bolus. Serum potassium returned at 2.2 mEq/L; ECG revealed large U waves. A vasopressin infusion was started at 0.04 U/min. Hypotension to systolic BP 70 was again observed, however this resolved with infusion of 900 mL of 20% IFE over 30 min. During this second IFE infusion the patient awakened and spontaneously opened her eyes, and additional sedation was required. Vasopressors were weaned off within 9 hours of initial IFE dosing and the patient was extubated neurologically intact 2 days later. Case discussion: HCQ overdose can manifest rapidly with severe cardiotoxicity. This patient exhibited toxicity consistent with HCQ with poor response to standard therapies. IFE has not been successfully described in the literature for use in this scenario. IFEfs proposed mechanism is mainly lipid sink, with efficacy relating to the drug's lipid solubility or the log P octanol/water partition coefficient. The log P of HCQ is 3, making it an ideal drug for IFE use. The use of IFE in this case was successful and could be considered for future overdose cases of HCQ. As the global burden of malaria is high exposures to HCQ are likely to continue. Conclusion: This case demonstrates the potential usefulness of IFE in the context of hydroxychloroquine poisoning.