Abstract A healthy 32-years-old man was admitted in emergency department after cardiac arrest at home. He had complaints of fatigue and general malaise after Pfizer-BioNTech Coronavirus disease-2019 (COVID-19) first dose vaccine 48 hours earlier. Upon hospital admission, patient scored 3 points in Glasgow Coma Scale. Electrocardiogram showed atrial fibrillation with rapid ventricular response and a point-of-care ultrasound demonstrated severe left ventricular dysfunction with global hypokinesia. Blood tests were remarkable for elevation of high-sensitivity cardiac troponin-T and inflammatory parameters, normal platelet and fibrinogen levels and slightly increased D-dimer. A computed tomography (CT) with angiography of the cerebral arteries revealed acute ischemic posterior circulation stroke with total occlusion of the basilar artery and partial occlusion of the left vertebral artery. Life-saving systemic thrombolysis was performed but there was no clinical benefit. Pulmonary embolism was excluded. Transesophageal echocardiography showed severe left ventricular dysfunction (LVEF 30%), global hypokinesia and an apical thrombus with no other significant abnormalities. De novo multiple ischemic injuries were shown in 24h control brain CT. Once autoimmunity, thrombophilia study, PCR and serologic tests for viral infections including SARS-CoV-2 were negative, cardioembolic stroke following post-vaccinal myocarditis was suspected. Brain stem death was verified 72h later and a post-mortem endomyocardial biopsy was performed, although no signal of myocarditis was found. COVID-19 mRNA vaccination is associated with increased risk of myocarditis. We report the first known case of cardioembolic stroke and probable myocarditis after BNT162b2 first dose. This highlights that, although rare and with a predominantly favorable course, vaccine-related myocarditis can have life-threatening complications. Figure 1Apical left ventricle thrombus on transesophageal echocardiography.