Abstract Background Uncontrolled Graves’ disease is associated with significant morbidity and mortality. Treatment of such patients who have developed multi-organ dysfunction is challenging, and novel interventions have to be explored. We present a case of uncontrolled thyrotoxicosis with cardiogenic shock and hepatic dysfunction successfully controlled using therapeutic plasma exchange as a bridge to definitive management with total thyroidectomy. Case Presentation Our patient is a 36-year-old Filipina with known Graves’ disease for three years but with poor compliance to medications. She was admitted due to one-month history of progressive bipedal edema, easy fatigability, palpitations, and increasing abdominal girth. On examination, she had hypotension, irregular cardiac rhythm at 120's, mild respiratory distress, jaundice, enlarged thyroid gland, decreased breath sounds, distended abdomen, and grade 2 bipedal edema. Work-up showed atrial fibrillation with rapid ventricular response, global hypokinesia, pericardial effusion, pulmonary edema, elevated liver enzymes and bilirubins, and dilated hepatic veins. The thyroid stimulating hormone was at 0. 014 uIU/mL (0.55-4.78 uIU/mL). Free T4 was at 2.54 ng/dL (0.89-1.76 ng/dL) and free T3 was at 4.1 pg/mL (2.30-4.20 pg/mL). Thyroid stimulating immunoglobulins (TSI) were positive at 7.59 IU/L (<0.10 IU/L). Ultrasound revealed an enlarged thyroid gland with increased vascular flow and a complicated cyst measuring 0.7×0.2×0.5 cm in the right lobe. The ongoing hepatic dysfunction precluded the use of thionamides. Radioactive iodine treatment was not considered because of its gradual effect and need for isolation which could not be done in a clinically unstable patient. Total thyroidectomy was deemed to be the best option for rapid and definitive management. Adequate pre-operative preparation was important to minimize the surgical risk. The patient was started on hydrocortisone. The medical team performed two sessions of therapeutic plasma exchange with fluid removal. The free T4 and free T3 levels decreased to 1. 0 ng/dL and 2. 04 pg/mL, respectively. The TSI level decreased to 1.45 IU/L. The liver function improved and the cardiac status stabilized. She was able to safely undergo total thyroidectomy on the ninth hospital day. Repeat 2D-echocardiogram done two days post-operatively showed improvement in ejection fraction from 33.7% to 53.1%. She was extubated three days after surgery, weaned off dobutamine within one week, and discharged nine days after surgery. Histopathology of the thyroid gland revealed papillary thyroid microcarcinoma in the right lobe. Conclusion Therapeutic plasma exchange, also known as plasmapheresis, is an extracorporeal blood purification technique that can remove circulating thyroid hormones and TSH-receptor antibodies. It's a novel treatment for complicated cases of thyroid storm but its utility is limited by cost, invasiveness, and lack of technical expertise. Our case report demonstrates that therapeutic plasma exchange is also an effective and safe treatment option for unstable patients who require rapid control of thyrotoxicosis prior to definitive treatment with thyroidectomy. Presentation: No date and time listed