We report a 75-year-old female with a history of hypertension who presented with a sudden onset of disorientation and aphasia. The patient was reported to had been administered with first dose of BNT162b2 COVID-19 vaccine (Pfizer–BioNTech) six days prior to admission, and for the first few days only complained of mild symptoms such as dizziness, headache and fatigue. The laboratory findings included platelet count of 11,000 per microliter, hemoglobin of 8.1g/dl, elevated level of creatinine level of 1.41 mg/dl, lactate dehydrogenase of 892 U/L (reference value, <214) d-dimer of 3.09 mg/L (reference value, < 0.71) and normal level of bilirubin and infection markers. Brain magnetic resonance imaging (MRI) showed multifocal tiny acute infarction in bilateral cerebral/cerebellar hemispheres. On the following day, the peripheral blood smear revealed anemia with schistocytes and increased level of microangiopathic hemolytic anemia (MAHA). Plasma exchange and intravenous steroid pulse therapy were initiated. She received packed red blood cells, platelet transfusions and underwent two rounds of plasma exchange but bicytopenia remained and neurological symptoms did not improve drastically. On day 11 after vaccine injection, she expired, first after having further deterioration of neurological signs and then further progression of metabolic acidosis. The ADAMTS13 (A Disintegrin And Metalloprotease with a ThromboSpondin Type 1 motif, member 13) activity was later revealed to have less than 0.5% activity (Reference value, > 40%), suggesting the diagnosis to be thrombotic thrombocytopenic purpura (TTP); which is an unprecedented case of TTP developed after vaccination with BNT162b2 mRNA COVID-19 vaccine.