Thrombosis with Thrombocytopenia Syndrome (TTS) or Vaccine-induced Immune Thrombotic Thrombocytopenia (VITT) had been reported in patients receiving the Ad26.COV2.S vaccination (Johnson & Johnson [J&J]/Janssen) vaccine. They frequently presented with cerebral venous sinus thrombosis (CVST), but venous or arterial thrombosis at other locations can be present. The majority of those affected are younger adult females. Therefore, after a brief pause from April 13–23, 2021, the Centers for Disease Control and Prevention (CDC) and the U.S. Food and Drug Administration (FDA) recommended caution in using this vaccine in females under 50 years. Based on the reported 28 cases of TTS after this vaccination (data till April 21, 2021) by CDC, 22 were females (78%), and 6 were male. None of those males had CVST but had thrombosis at other locations. We report the first case of a young male with TTS and CVST following Ad26.COV2.S vaccine presented with severe headache and diagnosed with acute right transverse and sigmoid cerebral venous sinus thrombosis, multiple right-sided pulmonary emboli, and right hepatic vein thrombosis. He was treated with parenteral anticoagulation with argatroban and intravenous immune globulin with the improvement of his symptoms. A heparin-induced thrombocytopenia with thrombosis (HITT) like syndrome caused by the genesis of a platelet-activating autoantibody against platelet factor 4 (PF4) triggered by adenoviral vector-based COVID-19 vaccinations is understood to be the underlying pathophysiology. TTS with CVST should be considered when patients present with headaches, stroke-like neurological symptoms, thrombocytopenia, and symptom onset 6–15 days after Ad26.COV2.S vaccination.

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